Lactococcus lactis: A Comprehensive Reference
1. Identity: Taxonomy, Chemical Characterization, and Natural Sources
1.1 Nomenclature and Taxonomic Classification
Lactococcus lactis is a gram-positive bacterium used extensively in the production of buttermilk and cheese, and has also become famous as the first genetically modified organism to be used alive for the treatment of human disease. The genus Lactococcus was proposed by Schleifer and colleagues in 1985 to reclassify some species of the genera Streptococcus (Lancefield group N lactic streptococci) and Lactobacillus. Before this reclassification, the organism was historically known as Streptococcus lactis. In 1873, Joseph Lister achieved the first pure culture isolation of a milk-fermenting bacterium from soured milk, naming it Bacterium lactis and demonstrating its specific causation of lactic acid fermentation, marking a milestone in bacteriology as one of the earliest uses of a bacterium as a model organism. By 1919, Sigurd Orla-Jensen reclassified it as Streptococcus lactis in his book The Lactic Acid Bacteria, based on its chain-forming, streptococcus-like morphology and lactic acid production from carbohydrates, integrating it into the emerging taxonomy of lactic acid bacteria.
As of 2021, Lactococcus lactis is classified into two subspecies: L. lactis subsp. lactis and L. lactis subsp. hordniae. Lactococcal cultures found in dairy fermentations are classified as subspecies cremoris, lactis, and lactis biovar diacetylactis. Within subsp. lactis, citrate-positive variants known as biovar diacetylactis are distinguished by their ability to ferment citrate, leading to the production of diacetyl, a key aroma compound responsible for buttery flavors in fermented dairy products. Note that the former subspecies cremoris, long used in scientific literature, has in recent taxonomic revisions been elevated to species level as Lactococcus cremoris, though many published studies still refer to it under the older designation L. lactis subsp. cremoris.
1.2 Morphological and Physiological Characteristics
L. lactis cells are cocci that group in pairs and short chains, and depending on growth conditions, appear ovoid with a typical length of 0.5–1.5 μm. L. lactis does not produce spores (nonsporulating) and are not motile (nonmotile). They have a homofermentative metabolism, meaning they produce lactic acid from sugars. They have also been reported to produce exclusive L-(+)-lactic acid; however, reported D-(−)-lactic acid can be produced when cultured at low pH. Lactococci are Gram-positive, catalase-negative, facultatively anaerobic, nonmotile, and non-spore-forming.
Phenotypically, it is classified as a gram-positive, spherical, homolactate, non-sporulating, and facultative anaerobic gut bacteria with hundreds of strains and biovariants published to date. Key desirable features of this organism include its generally recognized as safe (GRAS) status, probiotic properties, the absence of inclusion bodies and endotoxins, surface display and extracellular secretion technology, and a diverse selection of cloning and inducible expression vectors. Several factors including its small-sized fully sequenced genome (2.3 Mbp), and the development of successfully compatible genetic engineering tools such as cloning and expression systems with customizable options, have rendered it a desirable model.
1.3 Natural Sources and Environmental Origins
Lactococcus lactis mainly originates from fresh vegetables, fruits, and even roots or cereals, but it also can come from the animal skin. As such, it can be found frequently as natural starters in many fermented food products. It is an organism of substantial economic importance, used extensively in the production of fermented foods, and is widely held to have evolved from plant strains. The domestication of this organism to the milk environment is associated with genome reduction and gene decay, and the acquisition of specific genes involved in protein and lactose utilization by horizontal gene transfer.
Strains that are isolated from raw milk or even non-dairy environments are referred to as "wild" lactococci. According to studies, wild lactococci isolated from dairy and non-dairy sources can produce particular flavors that are different from those of industrial strains. Many research works report that the Lc. lactis population represents a part of the lactic acid bacteria population involved in the making of cassava-derived food products made in Africa, such as sour starches.
L. lactis is the main constituent of dairy starter culture systems used worldwide for the production of numerous fermented dairy products including cheese of both artisanal and commercial origin, and fermented milks such as buttermilk and sour cream. Through the consumption of fermented dairy products, it is estimated that humans ingest up to 1018 lactococcal cells per annum.
1.4 Common Forms and Preparations
L. lactis is encountered in several distinct forms depending on the intended application:
- Live/viable probiotic preparations: The dietary supplements used in clinical studies have included hard capsules containing L. cremoris FC. These are formulated to maintain bacterial viability through the gastrointestinal tract.
- Postbiotic / heat-inactivated preparations: Certain strains are used in postbiotic preparations, including heat-treated or inactivated forms that retain biologically active cell components. Unlike live probiotics, postbiotic preparations of Lactococcus lactis contain non-viable bacterial cells or their metabolites. These components, such as peptidoglycans, lipoteichoic acids, and other cell wall fragments, may interact with pattern recognition receptors in the gut, including toll-like receptors.
- Fermented dairy foods: L. lactis subsp. lactis (formerly Streptococcus lactis) is used in the early stages for the production of many cheeses, including brie, camembert, Cheddar, Colby, Gruyère, Parmesan, and Roquefort.
- Genetically engineered therapeutic strains: The use of Lactococcus lactis in novel biomedical applications is a fast-evolving area of interest. Quite distinct from its traditional use in the dairy industries, L. lactis has emerged as a potential delivery vector for various antigens as well as therapeutic and immunomodulatory proteins.
- Immobilized / food-matrix forms: Research has evaluated L. cremoris immobilized on oat flakes as a non-dairy probiotic product delivery system, though twelve-week consumption of Lactococcus cremoris spp. immobilized on oat flakes resulted in improvements in inflammatory, metabolic, and stress-related biomarkers, though further research is needed to confirm their efficacy and clarify their underlying mechanisms.
2. Traditional and Historical Use
Though Lactococcus lactis was not isolated and named until the late 19th and early 20th centuries, its presence in fermented dairy is ancient. Traditional cheese-making practices across Europe and parts of Asia relied on spontaneous fermentation driven by lactic acid bacteria naturally present in raw milk. L. lactis was unknowingly cultivated in these processes, especially in fresh and soft cheeses such as Neufchâtel, Cheddar, and farmer's cheese, where it initiated acidification and shaped flavor and texture.
For millennia, these fermented foods were not just dietary staples but also valued as health-promoting. Sour milk and cultured dairy products were used in folk medicine to support digestion, ease gastrointestinal issues, and strengthen immunity. In Ayurvedic and Greco-Roman traditions, fermented milk was regarded as a nourishing and therapeutic substance, frequently given to children, the elderly, and the ill.
For a very long time, L. lactis has been utilized in milk fermentation, both in well-managed industrial applications and small-scale traditional operations. Strains have been isolated from a variety of traditionally fermented foods, specifically from shubat, yogurts, dairy cake, acid porridge, sour cream, koumiss, dried milk cake, milk, cheese, goat's yogurt, goat's milk, fan acid whey, and jiaoke — spanning geographically diverse regions.
Other uses that have been reported for this bacterium include the production of pickled vegetables, beer or wine, some breads, and other fermented foodstuffs like soymilk kefir, buttermilk, and others.
The strain designated Lactococcus lactis subsp. cremoris (now L. cremoris) FC is a lactic acid bacterium that was originally isolated from a fermented milk of the Caucasus mountain region. This geographic region, which spans parts of what are today Russia, Georgia, and neighboring countries, has longstanding traditions of fermented dairy consumption associated with purported longevity and health benefits.
It must be emphasized that throughout this history, the organisms now identified as L. lactis were not recognized as discrete microbiological entities by the cultures that used them. The health-promoting reputations of fermented milks and cheeses were attributed to the foods themselves, not to specific bacterial strains. The scientific identification and characterization of L. lactis as the primary active agent in these fermentations is a product of modern microbiology.
3. Key Constituents and Mechanisms of Action
3.1 Lactic Acid Production
When L. lactis subsp. lactis is added to milk, the bacterium uses enzymes to produce energy molecules (ATP) from lactose. The byproduct of ATP energy production is lactic acid. The lactic acid produced by the bacterium curdles the milk, which then separates to form curds that are used to produce cheese. The capability to produce lactic acid is one of the reasons why L. lactis is one of the most important microorganisms in the dairy industry. This homofermentative acid production also underlies food preservation by lowering pH and inhibiting competing microorganisms.
3.2 Bacteriocins: Nisin and Related Antimicrobial Peptides
One of the most scientifically studied active compounds produced by L. lactis strains is nisin, a ribosomally synthesized antimicrobial peptide. Nisin is an antimicrobial peptide which belongs to the lantibiotic class of bacteriocins (Class I) and has been employed as a food preservative in over 50 countries. It is produced only by certain strains of Lactococcus lactis, which are extensively characterized bacteria used in the production of many fermented foods. It has a relatively wide antimicrobial spectrum and can inhibit the proliferation of most gram-positive bacteria. Nisin is heat stable and active at low pH, which makes it a good candidate for a natural food preservative.
Lantibiotics, including nisin, can have multiple mechanisms of action facilitated through the binding of lipid II and insertion into bacterial membranes. While nisin A was first discovered in 1928 in fermenting milk cultures, lantibiotics are characterized by the presence of unusual amino acid residues, including the lanthionines which give these peptides their name. Lantibiotics, including nisin, can have multiple mechanisms of action facilitated through the binding of lipid II and insertion into bacterial membranes.
Beyond nisin, L. lactis strains produce additional bacteriocins. An increasing number of bacteriocins, antimicrobial peptides synthesized by bacteria, including the lactococcal lantibiotics nisin and lacticin 3147 and the nonlantibiotic lactococcin 972 (Lcn972), have been reported to inhibit cell wall biosynthesis by binding to the cell wall precursor lipid II. Lactococcin B (LcnB) represents another class: purified LcnB has a bactericidal effect on sensitive L. lactis cells by dissipating the proton motive force and causing leakage of intracellular substrates. The activity of LcnB depends on the reduced state of the Cys-24 residue. Uptake and efflux studies of different solutes suggest that LcnB forms pores in the cytoplasmic membrane of sensitive L. lactis cells in the absence of a proton motive force.
3.3 Cell Wall Components and Immunomodulatory Constituents
Cell wall components, such as peptidoglycans, lipoteichoic acids, and other cell wall fragments, may interact with pattern recognition receptors in the gut, including toll-like receptors. Through this interaction, they can help support normal immune signaling pathways and mucosal immune balance. Some research suggests that specific strains may influence plasmacytoid dendritic cells, which play a role in antiviral defense and the production of interferons.
3.4 Exopolysaccharides and Metabolic Products
Many traits in lactococci that render these microorganisms suitable for dairy fermentations are encoded on plasmids. Indeed, traits such as lactose utilization, casein breakdown, bacteriophage resistance, bacteriocin production, and exopolysaccharide production have all been associated with extrachromosomal plasmid DNA. Lactic acid bacteria have been associated with a variety of products, including short-chain fatty acids, amines, bacteriocins, vitamins, and exopolysaccharides during metabolism. These metabolic outputs collectively contribute to the biological activities ascribed to L. lactis in the gut environment.
3.5 Anti-inflammatory Cytokine Delivery (Engineered Strains)
Interleukin-10 (IL-10) is one of the most important anti-inflammatory cytokines involved in the intestinal immune system, and because of its immunosuppressive activity and its central role in downregulating inflammatory cascades, it presents itself as a good therapeutic candidate against IBD. Genetically engineered strains of L. lactis have been constructed to secrete human IL-10 directly at the intestinal mucosa. This is a research-stage application and distinct from conventional probiotic or food use.
4. Scientific Evidence by Area of Use
4.1 Gastrointestinal Health and Constipation
The most robust human clinical evidence for L. lactis (specifically the cremoris FC strain) as a dietary supplement concerns its effects on defecation frequency. Researchers previously reported the probiotic effects of fermented milk made with L. cremoris FC on defecation and intestinal microflora in healthy adults based on a double-blind placebo-controlled study, and detected L. cremoris FC in the feces of subjects up to two weeks after administration, suggesting that the bacteria can reach the intestines in a viable form. Moreover, hard capsules containing L. cremoris FC were reported to affect defecation and intestinal microflora in healthy adults based on a double-blind placebo-controlled study.
A subsequent dose-escalation study addressed the effective dose: Twenty-seven subjects were recruited and consecutively ingested a placebo and two dose levels of L. cremoris FC (dose level 1, 1 × 107 CFU; dose level 2, 2 × 107 CFU) capsules daily for two weeks. Frequency of defecation (times/week) was significantly increased by dose level 2, and stool volume (units/week) was significantly increased by dose level 1. Overall, the results demonstrated that intake of a supplement containing at least 1 × 107 CFU L. cremoris FC improves defecation frequency and stool volume. Thus, L. cremoris FC could be considered a probiotic that is beneficial for defecation in healthy adults.
A larger, double-blind, placebo-controlled study using freeze-dried powder formulations extended these findings: Eighty-three participants were randomized into four groups with different doses: 50, 75, and 100 mg of freeze-dried FC (test) or corn starch (placebo). Defecation frequency significantly increased in all test groups compared to the placebo group. Stool appearance and volume were improved considerably within the groups administered 50 mg and 75 mg of FC. The abundances of total bacteria, Bifidobacterium spp., and Lactobacillus group in the feces showed increasing trends in the test groups. Regarding immunological parameters, the naïve T cell counts in the blood were significantly higher at a dose of 75 mg of FC in the test group than in the placebo group. These results suggest that FC intake improves defecation and some immunological parameters, especially naïve T cell counts, in healthy adults.
Evidence strength: Moderate. Multiple small-to-medium sized randomized, double-blind, placebo-controlled trials in healthy adults support a consistent effect on defecation frequency for the specific L. cremoris FC strain. Studies are short in duration (two to twelve weeks) and limited to healthy subjects with mild constipation. Generalizability to clinical constipation disorders is not established.
4.2 Immune Modulation
Lactococcus lactis spp. cremoris has been associated with promising immunomodulatory results in preclinical trials. The aim of one registered clinical study was to investigate the pharmacodynamic (PD) effects of three monoclonal microbial formulations of L. lactis spp. cremoris (EDP1066) on the immune response to keyhole limpet hemocyanin (KLH). Potential effects on the gut microbiota were also investigated.
Eighty-one healthy subjects (median age 28, range 18–59 years) were randomized to 28 days of enteric-coated capsules at five doses (n = 13) (1.5 × 1012 total cells daily), freeze-dried powder at one dose (n = 12) (3.0 × 1011 total cells daily) or five doses (n = 12), minitablets at one dose (n = 12) or five doses (n = 12), or placebo (n = 20) prior to KLH immunization. Although circulating Tregs as a percentage of CD4+ T cells were significantly increased in subjects treated with the 5× Powder formulation compared to placebo, the overall immunological signal was formulation-dependent and the primary endpoints were not uniformly met across all arms.
In preclinical research, independent research has shown that L. lactis spp. cremoris restored T-cell impairment in aged mice, and coadministration of L. lactis spp. cremoris with Lactobacillus paracasei spp. paracasei relieved atopic dermatitis symptoms, decreased serum IgE concentration, and rebalanced the population of Th1/Th2 cells in an atopic dermatitis mouse model.
Evidence strength: Preliminary to moderate for immunomodulation. Human evidence from the EDP1066 trial exists but results are mixed across formulations and no definitive clinical endpoint has been confirmed. Preclinical (animal and in vitro) evidence is more extensive but cannot be directly extrapolated to human benefit.
4.3 Skin Health and Atopic Dermatitis
Several strain-specific clinical studies have examined L. lactis and its effects on skin. A randomized, double-blind, placebo-controlled study registered on ClinicalTrials.gov (NCT03542994) evaluated EDP1066 — a preparation of L. lactis spp. cremoris — in participants with mild to moderate psoriasis and atopic dermatitis. Preclinical data of EDP1066 on both in vitro immune cell cultures and in vivo murine immune challenge and disease models show promising results; however, these data are not currently available in the public domain. Separately, a randomized study of Lactococcus lactis strain T21 assessed effects on skin condition in human volunteers, evaluating endpoints including trans-epidermal water loss (TEWL), skin brightness, and redness. The study applied an 8-week intervention design with validated dermatological scoring instruments; however, detailed efficacy results were not fully reproducible from available public abstracts at time of writing.
Evidence strength: Weak to preliminary in humans. Animal models show reductions in atopic dermatitis severity markers and IgE levels, but the volume of published, peer-reviewed randomized controlled trials in human subjects with atopic dermatitis attributable exclusively to L. lactis strains remains small.
4.4 Inflammatory Bowel Disease (IBD) — Engineered Strains
The use of LAB to prevent and treat inflammatory-related diseases was performed for the first time with a recombinant strain of Lactococcus lactis, the model LAB, producing and delivering IL-10 in situ, in different mouse models of colitis. Mucosal administration of recombinant L. lactis secreting IL-10 reduces 50% of the colitis induced by the administration of dextran sodium sulfate (DSS) in mice.
This preclinical success led to human Phase I investigation: Crohn's disease patients were treated with genetically modified Lactococcus lactis (LL-Thy12) in which the thymidylate synthase gene was replaced with a synthetic sequence encoding mature human interleukin-10. A biologically contained L. lactis strain secreting human IL-10 was constructed and used in a Phase I, open-label clinical trial. That trial demonstrated that treating CD patients with this strain is realistic and safe.
Systemic treatment of CD patients with interleukin-10 (IL-10) lacks clinical efficacy, but studies in animal models suggest that the topical application of IL-10, using living genetically modified bacteria, can reduce disease activity. The Phase I trial was designed to assess safety and biological containment; it was not powered to demonstrate efficacy. Results clearly hold promise for the safe application of live genetically modified L. lactis as an efficient therapeutic tool in human beings with chronic intestinal inflammation, but this application remains investigational and should be understood as a distinct category from conventional probiotic supplementation.
Evidence strength: Preliminary in humans for IBD. The genetically engineered IL-10-secreting strain has only been studied in a Phase I safety trial. Conventional (non-engineered) L. lactis strains for IBD lack direct robust randomized controlled trial evidence in humans.
4.5 Gut Microbiota Modulation
Relatively less is known about the probiotic activity of lactococci, as they have not been traditionally considered natural inhabitants of the human gastrointestinal tract. However, several studies have shown the possibility of lactococci residing in the human or animal gastrointestinal tract, and Lactococcus lactis has been isolated from the human intestinal tract. In the double-blind placebo-controlled supplementation study using freeze-dried FC at 50–100 mg doses, the abundances of total bacteria, Bifidobacterium spp., and Lactobacillus group in the feces showed increasing trends in the test groups. In a recent clinical trial, the consumption of a supplement containing L. cremoris was found to enhance not just the frequency of bowel movements and the composition of intestinal microbiota, but also various immunological parameters.
Evidence strength: Preliminary. Microbiota composition shifts have been documented in small human trials, but the magnitude, consistency, and clinical significance of these changes are not well established.
4.6 Anti-infective / Antimicrobial Activity (Bacteriocin-Mediated)
This area concerns the capacity of L. lactis-produced bacteriocins, particularly nisin, to inhibit pathogenic microorganisms. Cell-free supernatant fluid from Lactococcus lactis A5 showed inhibitory activities against both gram-positive pathogens (Bacillus cereus and Staphylococcus aureus) and gram-negative pathogens (Salmonella typhimurium). Nisin is predominantly active against gram-positive bacteria, and to act against gram-negative bacteria such as Escherichia coli or Salmonella species, it should be used in conjunction with chelating agents like EDTA or physical treatments like sub-lethal heat, osmotic shock, and freezing, which damage the outer membrane of the cell.
Evidence strength: Well established in vitro and in food science contexts; less explored as a direct health benefit in human clinical supplementation studies. The antimicrobial activity of nisin is the basis for its approval as a food preservative in over 50 countries, but its in vivo clinical utility in humans as a probiotic-mediated outcome is not well characterized.
4.7 Vaccine and Antigen Delivery (Engineered Strains)
Genetically modified Lactococcus lactis bacteria have been engineered as a tool to deliver bioactive proteins to mucosal tissues as a means to exert both local and systemic effects. They have an excellent safety profile, the result of years of human consumption in the food industry, as well as a lack of toxicity and immunogenicity. Containment strategies have been developed to promote further application as clinical protein-based therapeutics. Researchers have reviewed technological advancements made to enhance the potential of L. lactis as live biofactories and discussed some examples of tolerogenic immunotherapies mediated by mucosal drug delivery via L. lactis. This remains a research and early-phase clinical application area.
5. Body Systems Associated with Lactococcus lactis
- Gastrointestinal system: Primary area of interaction; lactic acid production, modulation of intestinal microbiota, effects on bowel motility and stool characteristics, and (for engineered strains) mucosal immune regulation in IBD.
- Immune system: Via interaction with toll-like receptors, modulation of dendritic cells, regulatory T cells (Tregs), and cytokine profiles including IL-10. Effects are strain-specific and studied across both innate and adaptive immune compartments.
- Integumentary system (skin): Preclinical and early clinical evidence for effects on atopic dermatitis markers, IgE levels, and skin barrier function via oral supplementation, mediated through gut-skin immune axis mechanisms.
- Mucosal immune system: Gut-associated lymphoid tissue (GALT) is the primary site of interaction; L. lactis does not colonize the gut permanently but exerts transient immunological effects during passage.
6. Dosage Forms and Reported Dosages
The following dosages are reported in peer-reviewed clinical studies. They are strain-specific and cannot be generalized across all L. lactis preparations.
- L. cremoris FC in hard capsules (defecation study): Twenty-seven subjects ingested dose level 1 (1 × 107 CFU daily) or dose level 2 (2 × 107 CFU daily) for two weeks. Defecation frequency was significantly increased at dose level 2, and stool volume was significantly increased at dose level 1.
- L. cremoris FC in freeze-dried powder (constipation/immune trial): Eighty-three participants were randomized into groups receiving 50, 75, or 100 mg of freeze-dried FC or placebo, with defecation frequency significantly increasing in all test groups compared to the placebo group.
- EDP1066 (L. lactis spp. cremoris) in immune modulation trial: Formulations tested included enteric-coated capsules at five doses (1.5 × 1012 total cells daily), freeze-dried powder at one dose (3.0 × 1011 total cells daily) or five doses, and minitablets at one or five doses, administered over 28 days.
- Genetically modified LL-Thy12 (Phase I IBD trial): Crohn's disease patients received genetically modified Lactococcus lactis (LL-Thy12), a biologically contained strain secreting human IL-10 — specific dose levels from this open-label Phase I trial were not available in the publicly accessible abstract.
No universally established daily dose exists for L. lactis as a general probiotic supplement; effective doses appear highly strain-specific, and the CFU or mass equivalents reported differ substantially across studies.
7. Safety Profile, Adverse Effects, and Notable Interactions
7.1 Regulatory Safety Status
Members of the Lactococcus genus are most commonly classed as Generally Recognized as Safe (GRAS). L. lactis cannot be considered an opportunist pathogen, as only two cases of endocarditis have been reported in the medical literature over a period of fifty years. In accordance with their traditional use in food, members of the L. lactis species have been listed in the "inventory of microbial food cultures" with documented use in food fermentations, and are most commonly classed as Generally Recognized as Safe (GRAS) by the Food and Drug Administration (FDA). Furthermore, L. lactis received from the European Food Safety Authority (EFSA) the status of Qualified Presumption of Safety (QPS), which is granted to those taxonomic groups deliberately introduced into the food chain that do not raise safety concerns.
Lactococcus lactis has been used for centuries in the fermentation of food, especially cheese, yoghurt, sauerkraut, and the like, thereby rendering its generally recognized as safe (GRAS) status by the Food and Drug Administration (FDA). L. lactis bacteria have been ingested even at high doses by healthy children, adults, elderly, as well as immune-compromised individuals and showed no health-compromising issues.
7.2 Opportunistic Infections: Case Reports
Despite its generally excellent safety record, L. lactis has been implicated in rare opportunistic infections. Over the last two decades, several cases of infections caused by Lactococcus lactis have been reported. This Gram-positive coccus is considered non-pathogenic for humans. However, in some rare cases, it can cause serious infections such as endocarditis, peritonitis, and intra-abdominal infections.
Lactococcus lactis has low virulence and is considered nonpathogenic. However, it has recently been considered an opportunistic pathogen microbe. A pathophysiological mechanism has been described to explain the virulence of this microorganism in the genesis of infectious endocarditis. Indeed, a study carried out in 2016 showed that Lactococcus lactis expresses the glycoprotein Cnm, which promotes its adhesion to type I collagen and to cardiac tissues (in particular the tissues of the aortic valve).
L. lactis is not considered a human pathogen, and human infections in people with immunosuppression or impaired defense mechanisms are opportunistic infections. Due to the rarity of the Lactococcus infection, the route of this infection is not well demonstrated. Hypotheses about the source of infection include exposure by ingestion or contact with unpasteurized dairy products or raw milk. Another proposed mechanism is direct intraluminal spreading from contaminated hands.
Documented in vitro antibiotic susceptibility data from a reported case: Drug susceptibility analysis results showed L. lactis subspecies lactis was susceptible to penicillin, ampicillin, tetracycline, vancomycin, linezolid, and levofloxacin; while resistant to erythromycin, ceftriaxone, and clindamycin; and mesomeric to gentamicin.
7.3 Safety of Genetically Modified Strains
Treatment of patients with a living, genetically modified bacterium raises questions about the safety of such a strategy for human subjects per se, as well as the biological containment of the transgene. Clinical trials demonstrated that the thyA-containment system was effective at restricting environmental dissemination and pharmacokinetic assessment confirmed an adequate formulation for human use was found. The pharmacokinetic profile of LL-IL10 was also tested in healthy and colitic mice and even in cases of severe intestinal inflammation (and therefore gut leakiness) no L. lactis were found in the circulation.
7.4 Known Limitations and Gaps in the Safety Literature
Lactococcus lactis is the primary organism for lactic acid bacteria (LAB) and is a globally recognized safe microorganism for the regulation of the intestinal micro-ecological balance of animals and improving the immune performance of the host. L. lactis is known to play a commercially important role in feed fortification, milk fermentation, and vaccine production, but pathogenic L. lactis has been isolated from many clinical cases in recent years, such as the brain of silver carp with lactococcosis, the liver and spleen of diseased waterfowl, milk samples and padding materials with cow mastitis, and blood and urine from human patients with endocarditis.
Relatively less is known about the probiotic activity of lactococci, as they have not been traditionally considered natural inhabitants of the human gastrointestinal tract, meaning that long-term colonization effects and interactions with established human microbiome communities are less well characterized compared to organisms such as Lactobacillus or Bifidobacterium species.
References
Go back