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Lactobacillus fermentum

Condiciones de Salud10
Tabla de contenidos

Otros Nombres

Bacillus casei deltaBacillus deltaBacterium gayoniBetabacterium JenseniiBetabacterium longumL. fermentumLactobacillus cellobiosusLactobacillus gayoniLactobacillus longusLactobacterium fermentumLactobacterium longumLimosilactobacillus fermentum

Sinopsis

Lactobacillus fermentum (Limosilactobacillus fermentum): A Comprehensive Reference

1. Identity, Classification, and Nomenclature

1.1 Current and Historical Names

The organism was first described by Beijerinck in 1901 and was formally placed on the Approved Lists of Bacterial Names in 1980 under the name Lactobacillus fermentum Beijerinck 1901. The species was formally reclassified into the new genus Limosilactobacillus in 2020 following a major genomic phylogeny study by Zheng et al., so that the current valid name is Limosilactobacillus fermentum. The name Lactobacillus fermentum remains widely used in the older clinical and scientific literature. A heterotypic synonym accepted under historical nomenclature is Lactobacillus cellobiosus Rogosa et al. 1953. The species is often abbreviated in the literature as L. fermentum, and individual strains carry additional designations such as CECT 5716, ME-3 (DSM 14241), PCC, and JDFM216, among others.

1.2 Taxonomic Position

Taxonomically, the species belongs to Phylum Firmicutes, Class Bacilli, Order Lactobacillales, Family Lactobacillaceae, Genus Lactobacillus, and falls within the obligately heterofermentative Group C lactobacilli, specifically the Lactobacillus reuteri phylogenetic group. The type strain is ATCC 14931, and the genome was fully sequenced for strain IFO 3956, with a genome size of 2.09 Mb. The species has a G+C content of 52–54 mol% and displays a d-aspartyl-l-ornithine-type peptidoglycan in its cell wall.

1.3 Morphological and Biochemical Characteristics

Cells are Gram-positive rods, measuring 0.5–0.9 × 3.0 µm, occurring singly or in pairs; they are non-motile; colonies are generally flat, circular or irregular to rough, often translucent, and typically non-pigmented, though rare strains produce a rusty orange pigment. The organism does not grow at 15 °C but is capable of growth at 45 °C. Lactobacillus fermentum, so named because it causes fermentation, is an obligately heterofermentative species. As a heterofermentative species, it produces multiple end products—primarily lactic acid, ethanol, and CO₂—during carbohydrate fermentation. The species uses several carbohydrates (arabinose, cellobiose, galactose, maltose, mannose, melibiose, raffinose, ribose, sucrose, trehalose, and xylose), though fermentation is strain-dependent; it has 52–54% G+C content.

1.4 Natural Ecological Sources

Lactobacillus species, including L. fermentum, populate nutrient-rich habitats, such as fermented plant matter and in animals (both vertebrates and invertebrates, including humans). Specific environments in which the species has been isolated and documented include:

  • Human breast milk: CECT5716 is a probiotic strain isolated from human milk, which is a good source for isolating probiotics for infants who cannot be exclusively breastfed.
  • Human gastrointestinal and urogenital tracts: Because it is of human origin, non-pathogenic, has high resistance to passing through the intestine, prevents pathogenic insults and promotes the maturation of the immune system, it has been identified as a potential probiotic.
  • Dairy fermented foods: L. fermentum may be used as a probiotic culture, and it is found as a member of the NSLAB (non-starter lactic acid bacteria) population in some cheese varieties (e.g., Comté, Ragusano); it is one of the most abundant species found in natural whey cultures for Caciocavallo Silano and Parmigiano Reggiano cheese.
  • African and West African fermented grain foods: Amylolytic strains of L. fermentum were isolated for the first time from Benin maize sourdough (ogi and mawè); subsequently, L. fermentum strains were described in various Nigerian traditional amylaceous fermented foods.
  • ME-3 strain origin: The strain L. fermentum ME-3 (DSM 14241) is a strain of human origin isolated from a healthy child.

1.5 Common Commercial Forms and Preparations

L. fermentum is available in various forms, including capsules and powders, and is often included in probiotic supplements to promote digestive wellness. In clinical research, the species has been delivered in several matrices:

  • Oral capsules containing freeze-dried viable bacteria (the predominant form in mastitis and adult supplementation trials)
  • Infant follow-on formula supplemented with the freeze-dried strain
  • Fermented dairy beverages such as kefir and goat's milk, used in certain cardiovascular and antioxidant studies

Probiotics are dosed by CFU (colony-forming units), not milligrams; many clinical trials of L. fermentum strains use 1 × 10⁸ to 1 × 10¹⁰ CFU/day, with a common single-strain trial dose around 1 × 10⁹ CFU/day.

2. Traditional and Historical Use

2.1 Presence in Ancient Fermented Foods

L. fermentum as a distinct microorganism was only identified in the 20th century, but its presence has long been embedded in the traditional use of fermented foods around the world; the bacterium thrives in fermented plant- and dairy-based foods, including sourdough bread, kimchi, fermented grains, yogurt, and fermented olives. Sourdough fermentation dates back thousands of years to ancient Egypt, and L. fermentum is one of the key microbial contributors to this process.

2.2 Traditional Uses in Africa and the Americas

Traditional fermented millet dough from West Africa has been an important source from which L. fermentum strains have been isolated and investigated for technological and probiotic properties. In Central and South America, traditional fermented maize beverages and porridges hosted this bacterium, even though people had no knowledge of its microbial identity; these preparations were given to children, the sick, and nursing mothers for digestion and nourishment. It is important to note that these were uses of fermented foods, not of the isolated bacterium—the organism was not identified or separated from its food matrix in these traditional contexts.

2.3 Transition to Modern Probiotic Science

Traditional use was food-based (fermented doughs, beverages, vegetables) rather than as an isolated probiotic ingredient; the species was isolated from fermented foods and human samples in the early 20th century and recognized among the lactic acid bacteria used in food microbiology; in the late 20th century, multiple strains were isolated and characterized for acid and bile tolerance and used in food technology; in the 2000s–2010s, clinical research expanded, with strains evaluated for mastitis prevention, infant and maternal health, antibiotic-associated diarrhea, upper respiratory tract infection reduction, and antioxidant effects.

3. Key Constituents and Active Compounds

3.1 Primary Metabolic Products

L. fermentum does not produce discrete "phytochemicals" in the plant-supplement sense, but rather exerts its bioactivity through a suite of microbial metabolites and structural components:

  • Lactic acid: L. fermentum is a lactic acid–producing bacterium; like other lactic acid bacteria, it converts carbohydrates into lactic acid and other organic acids, lowering local pH to discourage pathogens.
  • Short-chain fatty acids (SCFAs): One mechanism of L. fermentum CECT5716 activity involves an increase in luminal SCFA levels; SCFAs serve as the main energy substrate for intestinal epithelial cells and ameliorate excessive immune responses associated with inflammatory bowel disease by promoting regulatory T-cells.
  • Bacteriocins: A number of L. fermentum strains produce bacteriocins, though they have a limited host range, usually acting against strains of L. fermentum and L. acidophilus. Specifically, the bacteriocin NQGPLGNAHR produced by L. fermentum shows anti-adhesive and bactericidal activity against Staphylococcus aureus. Genomic analyses of L. fermentum strains have identified three antimicrobial peptides showing greater than 98% sequence identity to experimentally validated bacteriocins.
  • Exopolysaccharides (EPS): L. fermentum-produced EPS have many health benefits and unique physicochemical properties; they are widely used in the food industry to improve viscosity, mouthfeel, and textural properties of foods. Genomic analysis has confirmed that beneficial traits of industrial and probiotic importance in L. fermentum include the production of flavor compounds, exopolysaccharide, acetoin, and butanediol.
  • Glutathione and antioxidant enzymes: The strain ME-3 (DSM 14241) is a strain of human origin with both antimicrobial and antioxidative functional properties, including the complete glutathione system.
  • B-group and K vitamins: Genes related to the biosynthesis of B-group and K vitamins have been identified in L. fermentum genomes, allowing its application for novel bio-enriched food production.
  • Organic acids: The antibacterial capacity of L. fermentum is related to protein and non-protein antibacterial components, such as bacteriocins, organic acids, hydrogen peroxide, and EPS generated by the strain; organic acids, including lactic acid, phenyl lactic acid, citric acid, and acetic acid, inhibit the growth of pathogenic bacteria by increasing their outer membrane permeability, altering intracellular osmotic pressure, and inhibiting DNA synthesis.

3.2 Established Mechanisms of Action

Strains of L. fermentum have been reported to exert probiotic properties due to the ability to improve gut microbiota composition, reduce blood cholesterol, modulate the intestinal immune system, stimulate the release of immunoglobulin A, reduce intestinal inflammation, and increase the activity of antioxidant enzymes.

Antioxidant pathway: Research with L. fermentum 016 demonstrates that the organism enhances the host's antioxidant capacity by activating the Nrf2–Keap1 signaling pathway, thereby alleviating oxidative stress damage. Metabolites positively correlated with the Lactobacillus OTU—including butanoate, lipoic acid, vitamin B6, and taurine—are well known to have antioxidative effects by preventing oxygen radical generation and activating the transcription factor Nrf-2, a master regulator of cellular detoxification and redox status; a number of studies have now shown that probiotics exert potent antioxidant capacity through the Nrf2 signaling pathway.

Gut microbiota modulation: Evidence in animal models indicates that L. fermentum reshapes the gut microbiota by increasing microbial diversity and the abundance of beneficial bacteria, while inhibiting the expansion of potential pathogenic bacteria.

Immune modulation: L. fermentum has been shown to interact with human immune cells and to modulate specific pathways involved in innate and adaptive immune processes in diverse inflammatory diseases. L. fermentum participates in immune regulation; many strains have demonstrated capacity to promote a Th1 response.

Tryptophan metabolism: Research indicates that L. fermentum supplementation reveals immunoregulatory capabilities with significantly altered gut microbiota composition and metabolic activities, particularly through enhancing tryptophan metabolism.

Anti-inflammatory effects in the gut: Treatment with L. fermentum CECT5716 has been demonstrated to result in amelioration of the inflammatory response by counteracting colonic glutathione depletion.

Mastitis-related antimicrobial action: Oral or intramammary administration of certain L. fermentum strains can decrease pathogenic colonization—notably Staphylococcus spp.—in breast ducts and reduce local inflammation; the molecular mechanism involves competitive exclusion, antimicrobial metabolites, biofilm interference, and local immune modulation (increased sIgA).

4. Scientific Evidence by Area of Use

4.1 Lactational Mastitis Prevention and Treatment

This is the area with the most robust clinical evidence for L. fermentum. The most extensively studied strain is CECT5716 (also commercially designated Lc-40).

Key RCT — mastitis prevention: A randomized, double-blinded controlled trial evaluated the preventive effect of oral administration of L. fermentum CECT5716 on mastitis incidence in lactating women; the trial included 625 women who had received a preventive dose of antibiotics in the context of delivery, recruited 1–6 days after childbirth and randomly assigned to groups; the probiotic group received 1 capsule/day containing L. fermentum 3 × 10⁹ CFU, while the control group received a placebo capsule containing maltodextrin; the intervention period was 16 weeks. The oral administration of L. fermentum CECT5716 during lactation decreased by 51% the incidence rate of clinical mastitis.

Key open-label comparative trial — mastitis treatment: An open-label study with three arms compared two strains of lactobacilli and antibiotics in 352 women with mastitis; L. fermentum CECT5716 or L. salivarius CECT5713 were administered at a dose of 9 billion CFU/day for 21 days (groups A and B); these strains were isolated from milk samples of the women in groups A and B respectively; a third group received antibiotic therapy. Probiotic supplementation was even more effective than antibiotic treatment in lowering bacterial count (Staphylococcus epidermidis, Staphylococcus aureus, and Staphylococcus mitis) in human milk. The women taking probiotics showed more improvement and had less recurrence of mastitis compared to the women taking antibiotics; the authors concluded that the probiotics represented efficient alternatives to antibiotics for treating infectious mastitis during breastfeeding.

Dose-ranging RCT — breast pain and Staphylococcus load: A randomized, double-blind, placebo-controlled clinical trial evaluated three different doses of L. fermentum CECT5716 to assess its ability to reduce the load of Staphylococcus in the breast milk of 148 women suffering from painful breastfeeding; three groups received the probiotic for 3 weeks at doses of 3, 6, or 9 billion CFU/day; a fourth group received maltodextrin as control; the primary outcome was Staphylococcus counts in breast milk.

Evidence strength: Multiple randomized controlled trials with consistent directional results. The prevention trial (n=625) is large and double-blinded. The treatment trial (n=352) is open-label, which introduces some limitation. Overall, the evidence for this indication is considered among the stronger areas for any single L. fermentum strain.

4.2 Infant Gastrointestinal and Respiratory Infections

Infant formula trial: The aim of a key study was to examine the effects of a follow-on formula containing L. fermentum CECT5716 on the incidence of infections in infants between the ages of 6 and 12 months; a randomized, double-blinded controlled study including infants at the age of 6 months was conducted; infants were assigned randomly to either follow-on formula supplemented with L. fermentum plus galactooligosaccharide (experimental group), or the same formula supplemented with only galactooligosaccharide (control group); the main outcome was the incidence of infections for the 6-month duration of the study. The intake of the probiotic-supplemented diet significantly reduced the incidence rate of gastrointestinal infections (46%) and of upper respiratory tract infections (27%) when compared to the control.

Cesarean-section infants (pooled analysis): Cesarean section disrupts the natural microbiota colonization process in infants, which might compromise immune system maturation, leading to a higher risk of infections; a pooled analysis evaluated the effect of L. fermentum CECT5716 on the incidence of gastrointestinal and respiratory infections in the cesarean-section infant subgroups (n=173) of three randomized clinical trials in which this probiotic strain was demonstrated to be safe and effective for preventing infections. There was a significant reduction of 73% in the incidence of gastrointestinal infections in cesarean-section infants receiving L. fermentum CECT5716.

Mother-to-infant transfer trial: The incidence of infections in infants was also evaluated in a randomized, double-blinded, placebo-controlled multicenter trial in which L. fermentum CECT5716 was administered to the mothers for 16 weeks; almost 300 mother–infant pairs were included; the results showed a significantly lower incidence of conjunctivitis in the infants whose mothers received the probiotic.

The ESPGHAN (European Society for Paediatric Gastroenterology, Hepatology and Nutrition) criteria for safety are met by L. fermentum CECT5716, and several clinical trials have confirmed the good tolerability and safety of an L. fermentum CECT5716-containing formula.

Evidence strength: Multiple randomized double-blinded controlled trials and a pooled analysis. The evidence for reduction of gastrointestinal infections in infants using CECT5716-supplemented formula is considered moderately strong, with consistent results across several independent trials. The magnitude of effects (46% reduction in GI infections, 73% in cesarean-section infants) is notable, though longer-term follow-up data remain limited.

4.3 Antioxidant Activity and Cardiovascular Risk Markers

The strain ME-3 (DSM 14241) has been the primary focus of research in this area.

Goat's milk fermentation trial (cardiovascular markers): Among results from human ME-3 clinical trials: 21 volunteers were assigned to two treatment groups—a control group ingested goat's milk and the test group ingested goat's milk with L. fermentum ME-3 for 21 days; consumption of fermented goat's milk improved anti-atherogenicity in healthy subjects, with a 16% reduction in oxidized LDL-cholesterol, a 20% decrease in 8-isoprostanes, a 49% increase in the ratio of glutathione to oxidized glutathione (GSH/GSSG), and a 26% increase in total antioxidant activity.

Kefir RCT (lipid profile): In a randomized controlled study, the possibility for regulation of plasma lipid profile using a kefir containing the antioxidative probiotic strain L. fermentum ME-3 (DSM 14241) was tested; the trial was performed in clinically healthy adults with borderline-high serum low-density lipoprotein-cholesterol and/or high serum triglyceride levels based on guidelines from the European Cardiology Society and European Atherosclerosis Society; 164 participants meeting the inclusion criteria were included.

Open-label pilot study (Reg'Activ Cholesterol formulation): An open-label preliminary study examined whether the Reg'Activ Cholesterol supplement—containing L. fermentum ME-3—had a positive influence on cardiovascular-inflammatory and diabetic parameters; 45 clinically asymptomatic participants consumed the supplement for 4 weeks; parameters measured were total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride, oxidized LDL, hsCRP, IL-6, and glycosylated haemoglobin (HbA1c%). The cardiovascular and diabetes risk profile of the participants improved significantly after 4 weeks of the intervention.

Evidence strength: Preliminary to moderate. The antioxidant and lipid-modulating data from ME-3 are mechanistically coherent and replicated across multiple delivery formats, but most individual trials are small (n=21 to n=164). The open-label pilot study (n=45) lacks a placebo control. Larger, placebo-controlled trials are needed before firm clinical conclusions can be drawn.

4.4 Immune Modulation and Influenza Vaccination Response

In one trial, subjects received either a probiotic (10 billion CFU) or a matching placebo daily for 2 weeks before and after vaccination; two weeks following vaccination, NK cells had increased in the probiotic group but not in the placebo group. Several preclinical studies have demonstrated the health-promoting effects of L. fermentum CECT5716 in models of gastrointestinal inflammation, psychological stress, hypertension, immunity, metabolic disease, and asthma; its positive effect on the microbiota in a synbiotic formulation was shown in various clinical trials investigating mastitis, influenza vaccination, respiratory tract infections, and gastroenteritis.

Evidence strength: Preliminary. The vaccination-response data are from a single trial with a short duration. Preclinical models are suggestive but cannot be directly extrapolated to human clinical outcomes.

4.5 Gut Inflammation and Bowel Disorders

Irritable bowel syndrome (IBS) is a widespread intestinal disorder, characterised by abdominal discomfort and pain, changed bowel habits, flatulence, and bloating. Preclinical data show activity in colitis models. In a dextran sulfate sodium-induced ulcerative colitis model, L. fermentum 016 supplementation revealed immunoregulatory capabilities with significantly altered gut microbiota composition and metabolic activities, particularly enhancing tryptophan metabolism; in the model, supplementation effectively mitigated weight loss, increased disease activity index, and alleviated diarrhea, rectal bleeding, and colon shortening; it also reduced colonic pathological damage and histological injury scores.

Evidence strength: Currently animal/in-vitro only for IBD and IBS endpoints. No large human RCTs have been published specifically for L. fermentum in IBD or IBS as of the time of writing. These preclinical findings are mechanistically plausible but require clinical validation.

4.6 Metabolic and Anti-Diabetic Properties

Experimental studies and some clinical trials have demonstrated that Limosilactobacillus fermentum strains can beneficially modulate the host antioxidant and anti-inflammatory system, resulting in the amelioration of glucose homeostasis in diabetic conditions. Although early studies have identified anti-diabetic properties in some L. fermentum strains, an in-depth systematic review focusing on L. fermentum strains as a potential anti-diabetic treatment had not been found in the available literature at the time of the most recent review.

Evidence strength: Weak to preliminary in humans. Most evidence is from animal models or small open-label human studies. The anti-diabetic and metabolic findings are promising but not yet sufficient to support firm clinical conclusions.

4.7 Oral and Vaginal Microbiome

In one study, a non-sporulating, catalase-negative, Gram-positive bacterium was isolated from the vagina of a pregnant woman and identified using 16S gene sequencing as L. fermentum; the cell-free supernatant of the bacterium showed antimicrobial activity in minute doses by well diffusion method; it was suggested that this species of Lactobacilli could be considered for use in improving genital microfloral defense against Gram-positive and Gram-negative bacteria.

Evidence strength: Very preliminary; most vaginal microbiome data are from small in-vitro or observational studies. Human intervention data are very limited.

4.8 Cognitive and Behavioral Effects

Previous studies revealed that the health-promoting effects of L. fermentum JDFM216 were mediated by a nuclear hormone receptor family and PMK-1 signaling cascade which regulates the oxidative stress response in C. elegans. Animal research (mice) with strain JDFM216 has suggested potential cognitive benefits, but this work is preclinical and cannot be extrapolated to humans without clinical confirmation.

Evidence strength: Animal/invertebrate model data only. No human clinical trials on cognitive outcomes have been published for this species.

5. Body Systems and Health Areas of Association

At least eight benefit domains for certain strains of L. fermentum have clinical or mechanistic support: mastitis prevention, upper respiratory tract infection reduction, gut barrier support, antibiotic-associated diarrhea mitigation, lipid modulation, antioxidant effects, oral health support, and symptomatic improvement in functional gastrointestinal disorders.

  • Mammary/lactation system: Prevention and treatment of lactational mastitis (CECT5716 — strongest clinical evidence).
  • Immune system: L. fermentum has been shown to interact with human immune cells and to modulate specific pathways involved in innate and adaptive immune processes in diverse inflammatory diseases.
  • Gastrointestinal system: Gut microbiota modulation, antibiotic-associated diarrhea, gastrointestinal infection prevention in infants, preclinical evidence in colitis models.
  • Respiratory system: Reduction in incidence of community-acquired upper respiratory tract infections in infants (CECT5716).
  • Cardiovascular system: Oxidized-LDL reduction, HDL increase, triglyceride lowering, paraoxonase-1 activity (ME-3 strain; preliminary human evidence).
  • Urogenital system: Early evidence of antimicrobial properties relevant to vaginal microbiome; presence in breast milk microbiome.
  • Metabolic system: Preliminary evidence for modulation of glucose homeostasis and insulin resistance in animal models and small human studies.

6. Dosage Forms and Dosages Reported in Clinical Studies

Probiotics are dosed by CFU, not milligrams; many clinical trials of L. fermentum strains use 1 × 10⁸ to 1 × 10¹⁰ CFU/day, with a common single-strain trial dose around 1 × 10⁹ CFU/day. The following strain-specific dosages have been documented in clinical trial literature:

  • CECT5716, mastitis prevention (RCT, n=625): The probiotic group received L. fermentum CECT5716 for 16 weeks at doses of 3 × 10⁹ CFU/day; the control group received a placebo of maltodextrin.
  • CECT5716, mastitis treatment (open-label, n=352): L. fermentum CECT5716 was administered at a dose of 9 billion CFU/day for 21 days.
  • CECT5716, breast pain dose-ranging RCT (n=148): Three groups received the probiotic for 3 weeks at doses of 3, 6, or 9 billion CFU/day.
  • CECT5716, nursing women RCT (infant health): The Lc40 group (n=139) received 1 capsule/day containing 3 × 10⁹ CFU Lc40; the control group (n=152) received 1 placebo (maltodextrin) capsule/day.
  • CECT5716, vaccination response trial: Subjects received either the probiotic (10 billion CFU) or a matching placebo daily for 2 weeks before and after vaccination.
  • ME-3 (Reg'Activ Cholesterol open-label study, n=45, 4 weeks): delivered via multi-ingredient supplement formula; 45 clinically asymptomatic participants consumed the RAC containing L. fermentum ME-3 for 4 weeks.
  • Infant formula delivery: Typical doses in infant studies approximate 8.4 × 10⁸ to 1 × 10⁹ CFU/day, delivered in formula.

Typical effective clinical doses used in trials range from 1 × 10⁸ to 1 × 10¹⁰ CFU/day. It is essential to note that dosages are strain-specific and cannot be generalized across all L. fermentum preparations. Trial protocols differ in delivery format, duration, and co-ingredients.

7. Safety Considerations and Interactions

7.1 Regulatory Safety Status

L. fermentum was included in the Qualified Presumption of Safety (QPS) list of the European Food Safety Authority (EFSA) in 2009, listed as a "generally recognized as safe" (GRAS) organism by the US Food and Drug Administration (FDA) in 2013, and included in the list of bacteria that could be used in food in China in 2011. Lactobacillus fermentum, which is commonly found in food products, is considered a "generally recognised as safe" (GRAS) organism by the US Food and Drug Administration and is on the European Food Safety Authority's list of biological agents with a "qualified presumption of safety" (QPS).

7.2 General Tolerability in Healthy Populations

L. fermentum is widely regarded as a safe probiotic strain; it apparently has no ill-effects, being consumed in a variety of fermented foods by people of different regions and ages. L. fermentum is generally well tolerated in healthy adults; most adverse effects are mild and gastrointestinal: transient GI symptoms (bloating, gas) occur in approximately 5–15% in some trials, loose stools in approximately 1–10%, and allergic reactions are rare (~0.1%).

Temporary gas, bloating, or stool changes during the first 3–7 days as the microbiome adjusts are the most commonly noted effects; these are usually self-limited, and taking with food or reducing the dose can help.

7.3 Strain-Level Variation in Safety Profile

An important scientific caveat concerns strain-level differences. Research has indicated that certain L. fermentum strains may decrease intestinal barrier integrity; the human oral isolate L. fermentum AGR1487 reduces in-vitro measures of intestinal barrier integrity. These findings illustrate that bacterial strains of the same species can cause contrasting host responses and suggest that food-safe status should be given to individual strains, not to the species as a whole. This is a key limitation: regulatory GRAS/QPS designations apply at the species level, but biologically relevant safety and efficacy properties are strain-specific.

7.4 Use in Vulnerable Populations

No established LD50 exists; very high CFU dosing can increase transient GI symptoms; in rare, vulnerable hosts, systemic infection is possible; in immunocompromised patients, signs may include fever or sepsis requiring immediate medical care. Although probiotic strains are naturally commensal bacteria and generally recognized as safe, there have been some safety risks associated with the use of specific strains; Lactobacillus may cause infections in immunocompromised patients. Immunocompromised individuals—those with neutropenia, advanced HIV, post-transplant status, or receiving chemotherapy—should consult their specialist before using any live microorganism.

For infants specifically, the ESPGHAN criteria for safety are met by L. fermentum CECT5716, and several clinical trials have confirmed the good tolerability and safety of an L. fermentum CECT5716-containing formula.

7.5 Interactions with Antibiotics

Live probiotics interact primarily through viability against antibiotics and by altering microbiome-dependent drug handling; most interactions are low risk except in immunosuppressed or critically ill patients; antibiotics such as amoxicillin-clavulanate, ciprofloxacin, and clindamycin may kill probiotic cells; the practical recommendation is to separate dosing by 2–4 hours and continue the probiotic during and 1–4 weeks after the antibiotic course.

7.6 Genomic Safety Assessment

Genomic analysis of L. fermentum strains has indicated that negative traits such as transmissible antibiotic resistance, pathogenicity, or virulence appear to be absent, suggesting the strain studied to be considered safe. However, this conclusion is strain-specific and cannot be uniformly applied to all isolates without individual genomic characterization.

8. Limitations and Notes on Evidence Quality

Benefits are strain-specific; it is important not to extrapolate a benefit from one L. fermentum strain to another. Several additional limitations apply across the body of evidence:

  • Most trials of individual strains are conducted by or in collaboration with the commercial developers of those strains (e.g., Biosearch Life for CECT5716), introducing potential conflicts of interest.
  • Many trials are of short duration (3–16 weeks), limiting conclusions about long-term safety or efficacy.
  • Future evaluations of the long-term health effects of L. fermentum CECT5716 may provide further insight into its use; more intervention studies in infants with longer observation periods will give further insights into its health-promoting effects.
  • The quality of available evidence is moderate, with ongoing research aimed at further elucidating its benefits and mechanisms of action.
  • Cardiovascular and antioxidant data for ME-3 largely derive from small trials and open-label designs; their clinical significance in larger, blinded populations remains to be established.
  • Most gut inflammation and metabolic data are from animal or in-vitro models and lack human RCT confirmation.

References

Condiciones de Salud

Condiciones de salud que Lactobacillus fermentum puede ayudar a apoyar.

  • Lactobacillus fermentum has demonstrated inhibitory activity against both Candida albicans and C. glabrata. It is identified in a 2024 comprehensive review of 25 clinical studies as an evidence-supported strain for vulvovaginal candidiasis management. A clinical strain isolated from human throat showed growth inhibition of both major Candida species.

  • Lactobacillus fermentum is among the Lactobacillus species studied for atopic dermatitis, with clinical evidence showing SCORAD improvements. A probiotic formulation including L. fermentum significantly improved SCORAD values in children with AD in published clinical studies.

  • Lactobacillus fermentum is a heterofermentative lactic acid bacterium found in fermented foods and the human gut with demonstrated probiotic effects including gut microbiota modulation, antioxidant activity, and cholesterol reduction. Several strains have been evaluated in human clinical trials for gut health.

  • Lactobacillus fermentum has been studied in probiotic combinations for cognitive improvement in Alzheimer's disease patients and is classified among psychobiotic Lactobacillus strains. It contributes to gut-brain axis function through GABA production, gut barrier integrity, and reduction of neuroinflammatory markers.

  • FlotadoresCientífico

    Lactobacillus fermentum is a lactic acid bacterium with evidence from clinical IBD studies as part of multi-strain probiotic products. It contributes to gut microbiota restoration and anti-inflammatory effects important in UC management.

  • GiardiaCientífico

    Lactobacillus fermentum CECT5716, isolated from human breast milk, has been shown in multiple RCTs to treat and prevent lactational mastitis. A 2010 RCT of 352 women found oral L. fermentum outperformed antibiotics for treating infectious mastitis, with greater improvement and lower recurrence. A 2017 RCT of 625 women found L. fermentum reduced mastitis incidence by approximately 51% versus control (p=0.021).

  • Lactobacillus fermentum has been evaluated in oral microbiome contexts and is documented in critical appraisals of probiotics for oral health. It is one of the Lactobacillus species identified as capable of modulating oral microbial composition and reducing cariogenic bacteria.

  • DeshidrataciónCientífico

    Lactobacillus fermentum is part of the vaginal Döderlein flora that directly influences urinary flora composition. It is noted in urogenital microbiome studies and was the original classification of the L. reuteri RC-14 strain proven in urogenital RCTs. In vitro studies demonstrate L. fermentum strains exhibit potent anti-adhesive properties against uropathogenic E. coli through competition, inhibition, and displacement, suggesting a protective role for urinary flora.

  • HipoCientífico

    Lactobacillus fermentum (including strain RC-14, now reclassified as L. reuteri RC-14) has been used in clinical trials for UTI prevention in women, acting as a urogenital probiotic that colonizes the vaginal tract after oral intake and inhibits uropathogen growth. Multiple RCTs document reduction in UTI recurrence with this organism in combination with L. rhamnosus GR-1.

  • DermatitisCientífico

    Lactobacillus fermentum (strain LF15) has clinical evidence for vaginal health; a vaginal tablet combining L. fermentum LF15 with L. plantarum LP01 restored vaginal pH acidity and reduced Nugent scores in BV patients. L. fermentum is a native vaginal isolate from healthy women and is included among lactobacilli with antimicrobial properties against urogenital infections. It is found in the healthy vaginal microbiome alongside other key lactobacilli.

Sistemas Corporales

Sistemas corporales que Lactobacillus fermentum puede ayudar a apoyar.

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