Lactobacillus acidophilus

Lactobacillus acidophilus

1. Identity, Taxonomy, and Natural Sources

Nomenclature and Classification

Lactobacillus acidophilus (Neo-Latin: acid-loving milk-bacillus) is a rod-shaped, Gram-positive, homofermentative, anaerobic microbe first isolated from infant feces in the year 1900. Its formal taxonomy was established by Johnson et al. in 1980 (Taxonomy ID: NCBI:txid1579), with the type strain designated ATCC 4356, DSM 20079, JCM 1132, and several other international culture collection accessions. A historical heterotypic synonym is Thermobacterium intestinale Orla-Jensen et al. 1936.

The organism sits within the classification: Bacteria; Bacillati; Bacillota; Bacilli; Lactobacillales; Lactobacillaceae; Lactobacillus. Taxonomically, L. acidophilus is part of a larger complex comprising several closely related species: Lb. acidophilus, Lb. amylovorus, Lb. crispatus, Lb. gallinarum, Lb. gasseri, and Lb. johnsonii.

The genus Lactobacillus was first proposed over a century ago in 1901 by M. W. Beijerinck. The species epithet acidophilus, meaning "acid loving," was so named because lactobacilli are historically isolated from the intestinal tract and vagina of humans and animals, where the environment can be quite acidic. The species name reflects a key physiological property: it most readily grows at low pH levels (below 5.0), and has an optimum growth temperature of 37 °C.

Note on nomenclature complexity: Initially proposed by Beijerinck in 1901, the genus Lactobacillus has experienced multiple taxonomical reassignments. Initially based on phenotypic traits, its taxonomic assignment criteria has been modified throughout the decades, primarily based on molecular approaches including 16S rRNA gene sequencing. Lactobacillus is a complex genus with highly variable phenotypic differentiation within clades and an ever-increasing number of new species and re-designations. This heterogeneity has since been studied as a whole, dividing the genus into 23 different genera. However, Lactobacillus acidophilus itself has retained its original classification through these reclassifications.

Common Strains

The strain of L. acidophilus that has been most widely researched and is most widely used as a probiotic is referred to as NCFM. Other commercially significant strains include La-14, DDS-1, LA-5, and LA85. Benefits, safety, and survival depend on specific strains rather than the species label alone.

Natural Habitats

L. acidophilus is a normal inhabitant of the gastrointestinal and genitourinary tracts. Since its original isolation by Moro in 1900 from infant feces, the organism has been found in the intestinal tract of humans, breast-fed infants, and persons consuming high milk-, lactose-, or dextrin-containing diets. In healthy humans, lactobacilli are normally present in the oral cavity (10³–10⁷ CFU/g), the ileum (10³–10⁷ CFU/g), and the colon (10⁴–10⁸ CFU/g), and they are the dominant microorganism in the vagina. The species also inhabits the gastrointestinal tracts of several other animal species including pigs, chickens, cattle, dogs, mice, rats, and hamsters.

Commercial Forms and Preparations

Commercial strains are isolated, genomically and phenotypically characterized, scaled in defined culture media under GMP conditions, concentrated by centrifugation, and stabilized by freeze-drying or spray-drying with cryoprotectants before formulation into capsules, sachets, dairy matrices, or vaginal suppositories. Strains of L. acidophilus are used in dairy products as probiotics and as flavor-contributing strains in certain dairy products such as yogurt, sweet acidophilus milk, and cheese. Potency is measured and expressed in colony-forming units (CFU). Enteric-coated or dairy-matrix delivery often increases survival to the intestine (enteric: approximately 20–60% recovery; non-coated: approximately 1–10%).

Analysis of commercial isolates spanning 92 years and including multiple strains demonstrated that L. acidophilus was a low-diversity, monophyletic species with commercial isolates essentially identical at the sequence level, indicating that commercial use has domesticated L. acidophilus with genetically stable, invariant strains being consumed globally.

2. Traditional and Historical Use

Ancient Fermented Foods

The use of fermented foods reflects an intimate relationship between humans and microorganisms, and lactobacilli in particular, stretching back over 8,000 years. Although precise attribution of L. acidophilus within ancient fermented preparations is impossible without modern microbiological methods, the species would have been present in the traditional fermented dairy foods consumed across Asia, the Middle East, and Europe throughout recorded history. The lactic acid bacteria are a group of Gram-positive bacteria united by their ability to produce lactic acid as a major end product of carbohydrate metabolism, which has resulted in their artisanal and industrial use in dairy fermentations.

Early Scientific History

Around the turn of the twentieth century, Nobel Prize winner Élie Metchnikoff was publicizing the idea that lactic acid bacteria from yogurt and fermented milk could help extend lifespan and improve gut health. Although Metchnikoff focused on Lactobacillus bulgaricus, his ideas paved the way for interest in L. acidophilus and related organisms. L. acidophilus was characterized in the early microbiology era; the species name emerged around 1900. Historically, Lactobacillus acidophilus is the Lactobacillus species most often implicated as an intestinal probiotic capable of eliciting beneficial effects on the microflora of the gastrointestinal tract.

L. acidophilus is a Gram-positive lactic acid bacterium that has had widespread historical use in the dairy industry and, more recently, as a probiotic. Although it has been designated as safe for human consumption, increasing commercial regulation and clinical demands for probiotic validation have resulted in a need to understand its genetic diversity. A history of safe consumption of lactobacilli is widely acknowledged, but more recently specific LAB strains associated with health benefits have been sold as probiotics, establishing a significant global market.

3. Key Constituents, Structural Features, and Active Compounds

Cell Architecture

As a live microorganism, L. acidophilus is composed of macromolecules including a peptidoglycan cell wall, membrane lipids, DNA/plasmids, and proteins. A notable structural feature distinguishing L. acidophilus NCFM from many other lactobacilli is the presence of a proteinaceous surface (S-) layer. The S-layer-forming bacterium L. acidophilus NCFM expresses three major S-layer proteins (Slps): SlpA (46 kDa), SlpB (47 kDa), and SlpX (51 kDa). SlpA has a demonstrated role in adhesion to Caco-2 intestinal epithelial cells in vitro.

Lactic Acid and Organic Acid Production

L. acidophilus can ferment hexoses, including lactose and more complex oligosaccharides, to produce lactic acid and lower the pH of the environment where the organism is cultured. Acidified environments — such as food matrices, the vagina, and regions within the gastrointestinal tract — can interfere with the growth of undesirable bacteria, pathogens, and yeasts.

Bacteriocins

Some lactobacilli and bifidobacteria can produce antimicrobial peptides known as bacteriocins, which prevent the proliferation of selected pathogens. Bacteriocins are small cationic molecules composed of approximately 30–60 amino acids. These molecules act at bacterial cytoplasmic membranes and target energized membrane vesicles to disrupt the proton-motive force. They are classified into four main types based on primary structures, molecular weights, post-translational modifications, and genetic characteristics. Compounds produced by L. acidophilus have been shown to inhibit the growth of Helicobacter, C. difficile, rotaviruses, and multidrug-resistant Shigella spp.

Bile Salt Hydrolases (BSHs)

The transformation of bile acids by the gut microbiota is increasingly recognized as an important factor shaping host health. The prerequisite step of bile acid metabolism is carried out by bile salt hydrolases (BSHs), which are encoded by select gut and probiotic bacteria. Bacterial BSHs cleave the conjugated glycine or taurine from bile acids, an essential upstream step for the production of deconjugated and secondary bile acids. Probiotic lactobacilli harbor a considerable number and diversity of BSHs; however, their contribution to Lactobacillus fitness and colonization remains incompletely understood.

Beta-Galactosidase (Lactase)

Commercial strains of L. acidophilus are characterized for acid and bile tolerance, adhesion factors (S-layer proteins), and enzymatic functions such as β-galactosidase and bile salt hydrolase; these properties determine clinical utility. Metabolically, the organism undergoes bacterial glycolysis (pyruvate → L-lactate), and its β-galactosidase activity hydrolyzes lactose.

Lipoteichoic Acid (LTA)

Co-culture of murine macrophages with L. acidophilus strain NCFM elicited an M2b-like phenotype associated with TH2 skewing and immune regulatory function. For NCFM, this M2b phenotype was dependent on expression of lipoteichoic acid and S-layer proteins. Toll-like receptor 2 (TLR2), the cytosolic nucleotide-binding oligomerization domain-containing 2 (NOD2) receptor, and the inflammasome-associated caspase-1 were identified as contributors to macrophage activation.

4. Mechanisms of Action

Competitive Exclusion and Colonization Resistance

On one hand, Lactobacillus can antagonize pathogenic bacteria infection in the intestine primarily through bacteriocin production, organic acids, and hydrogen peroxide; on the other hand, commensal organisms contribute to colonization and intestinal function. The term "colonization resistance" refers to the use of probiotics to prevent or treat enteric pathogens.

Bile Acid Metabolism and Cholesterol Effects

The synthesis of bile salt hydrolase is a key feature of some Lactobacillus species, which may alter the activation of farnesoid X receptor signaling and hepatic lipid metabolism. The proposed mechanism includes bile salts degradation through the action of microbial BSH, making them relatively less soluble and thus reducing their reabsorption by the intestinal epithelial layer and increasing their excretion in feces. Additionally, bacterial bile salt hydrolase activity and assimilation of cholesterol in vitro may reduce enterohepatic reabsorption of bile acids, increasing cholesterol catabolism to synthesize bile acids; some lactobacilli can also incorporate cholesterol into cell membranes.

Immune Modulation via S-Layer Protein A (SlpA)

Interactions of L. acidophilus NCFM and its cell surface compounds with dendritic cells (DCs) have been examined. L. acidophilus NCFM attached to DCs and induced a concentration-dependent production of IL-10 and low IL-12p70. The bacterium binds to DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), a DC-specific receptor. A knockout mutant of L. acidophilus NCFM lacking the surface (S) layer A protein (SlpA) was significantly reduced in binding to DC-SIGN. SlpA has a demonstrated role in adhesion to Caco-2 intestinal epithelial cells in vitro and has been shown to modulate dendritic cell and T-cell functionalities with murine DCs.

Intestinal Barrier Enhancement

L. acidophilus induces a strain-specific and Toll-Like Receptor 2-dependent enhancement of intestinal epithelial tight junction barrier and protection against intestinal inflammation. Enhancement of tight junction protein expression and mucin production strengthens the epithelial barrier and reduces translocation of luminal antigens.

Transience of Colonization

The primary elimination route is fecal passage; persistence is typically transient, often declining to baseline within days to weeks after discontinuation. There is no defined half-life as with small molecules; steady-state presence requires ongoing dosing. Detectable fecal recovery often declines within days to 1–4 weeks after stopping supplementation.

5. Scientific Evidence by Area of Use

5.1 Acute Infectious Diarrhea (Pediatric)

A systematic review and meta-analysis included a total of 15 RCTs involving 1,765 patients. Compared with placebo or no treatment, L. acidophilus was associated with a reduced duration of diarrhea (moderate quality of evidence), but the effect was not statistically significant when only the individual probiotic strain was provided. L. acidophilus was effective when used at a daily dose ≥ 10⁹ CFU. L. acidophilus reduced the frequency of diarrhea on day 2 to day 5, with statistical significance on day 3. When administered at a dosage of more than 10⁹ CFU to children with acute gastroenteritis, moderate- to low-quality data showed that L. acidophilus reduced the duration of diarrhea and conferred a benefit for frequency of diarrhea.

A systematic review and meta-analysis of controlled clinical trials documented that the use of L. acidophilus LB, compared with placebo, reduces the duration of diarrhea associated with acute gastroenteritis in hospitalized infants. The European Society of Pediatric Gastroenterology, Hepatology, and Nutrition recommends the use of L. acidophilus LB in the management of acute diarrhea. However, the American Gastroenterological Association (AGA) suggests avoiding the use of probiotics in children with acute infectious gastroenteritis (conditional recommendation). Guideline recommendations thus differ by region and body, and are based on moderate- to low-quality evidence.

5.2 Antibiotic-Associated Diarrhea (AAD)

L. acidophilus LB is effective and safe as an adjuvant in the treatment of acute diarrhea, chronic diarrhea, and antibiotic-associated diarrhea, even in the presence of immunosuppression. A recent RCT examined strain LA85 specifically: this randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of L. acidophilus LA85 in preventing amoxicillin-associated diarrhea. A total of 82 adult participants receiving amoxicillin treatment were randomized to receive either LA85 (2 × 10⁹ CFU/day) or placebo for 14 days, with primary outcomes including AAD incidence, diarrhea duration, and stool consistency. LA85 supplementation was associated with a trend toward a reduction in the incidence of AAD; however, this difference did not reach statistical significance. Nonetheless, LA85 notably shortened the duration of diarrhea episodes compared to placebo (p = 0.072), suggesting a clinically meaningful improvement. The evidence for AAD prevention is promising but, for individual strains of L. acidophilus, remains preliminary and often based on small trials.

5.3 Irritable Bowel Syndrome (IBS)

A randomized controlled trial (Nutrients, 2020) reported that Lactobacillus acidophilus DDS-1 and Bifidobacterium lactis UABla-12 improved abdominal pain severity and symptomology in irritable bowel syndrome. A placebo-controlled randomized clinical trial also evaluated a 2-strain mixture of L. acidophilus in the treatment of IBS (Dig Liver Dis, 2020). However, one study tested two different doses (10¹⁰ CFU/day and 10⁹ CFU/day) of Lactobacillus acidophilus NCFM and reported that none of the outcomes showed a statistically significant effect. Probiotics may modulate gut motility, reduce visceral hypersensitivity, alter fermentation patterns, and reduce low-grade mucosal inflammation that contributes to IBS symptoms. Overall, the IBS evidence for L. acidophilus specifically is mixed; many positive trials have used multi-strain formulations, making it difficult to attribute effects to L. acidophilus alone.

5.4 Lactose Intolerance

Preclinical studies have found that L. acidophilus supplementation may assist in breaking down lactose; however, dedicated human clinical trials evaluating its efficacy in alleviating symptoms related to lactose intolerance have been limited. One randomized, double-blind, placebo-controlled crossover study examined the DDS-1 strain: the results suggested that although no significant changes were observed for the hydrogen breath test (HBT), the DDS-1 strain of L. acidophilus can help improve gastrointestinal symptoms of lactose intolerance such as diarrhea, abdominal cramping, and vomiting. Longitudinal evaluation found the group receiving the placebo to have worsened symptoms on lactose challenge at 4 weeks compared with the group receiving DDS-1. However, data on HBT, stool form, and the SF-12 quality of life survey did not yield statistically significant results. Evidence in this area is preliminary.

5.5 Vaginal Health (Bacterial Vaginosis and Vulvovaginal Candidiasis)

Healthy vaginal microbiota is often dominated by Lactobacillus spp.; L. acidophilus (some strains) may help reestablish and maintain a lactobacilli-dominant community, lowering vaginal pH and inhibiting overgrowth of BV-associated anaerobes. Clinical research has evaluated the La-14 strain: the probiotic strains L. acidophilus La-14 and Lacticaseibacillus rhamnosus HN001 have shown beneficial effects for vaginal health in randomized placebo-controlled clinical trials — including elevating vaginal L. acidophilus and L. rhamnosus levels, reducing Nugent score (reflecting an increase in vaginal lactobacilli), and alleviating BV- and vulvovaginal candidiasis (VVC) associated symptoms. Successful restoration of Lactobacillus-dominated composition in BV patients was reported with a lower recurrence rate along with significant decreases in BV-related bacteria such as Gardnerella, Prevotella, Megasphaera, Coriobacteriaceae, and Atopobium. The evidence for vaginal health applications is encouraging but based on a limited number of trials, many of which use combination products.

5.6 Cholesterol and Lipid Metabolism

Great attention has been given to lactobacilli due to their effectiveness in modulating lipid metabolism, with serum cholesterol-level reduction occurring by means of bile salt hydrolase activity that has a direct impact on the host's bile salt metabolism, accounting for the formation of deconjugated bile acids. L. acidophilus has been shown in studies to provide a variety of probiotic benefits including decreasing cholesterol and promoting immunological function. However, much of the positive cholesterol data for L. acidophilus specifically comes from animal models or mixed-species trials. Probiotics interact with bile acids in the gut lumen, modifying bile acid metabolism and in turn influencing cholesterol absorption. Human clinical evidence for L. acidophilus as a standalone cholesterol-lowering agent remains limited, and results are not yet consistent across trials.

5.7 Immune Modulation and Respiratory Infections

L. acidophilus augments mucosal IgA and modulates dendritic cells and regulatory T-cell (Treg) pathways; RCTs show modest reductions in upper respiratory tract infection (URTI) incidence and duration in some populations. The immune-modulatory mechanism has been characterized in vitro and in animal models: L. acidophilus NCFM attached to DCs and induced a concentration-dependent production of IL-10 and low IL-12p70, and it was demonstrated that the bacterium binds to DC-SIGN, a DC-specific receptor. Evidence in humans for respiratory infection prevention is preliminary and is typically derived from multi-strain probiotic trials rather than trials of L. acidophilus in isolation.

5.8 Inflammatory Bowel Disease (IBD)

Dysbiosis, a loss of balance between resident bacterial communities and their host, is associated with multiple diseases, including inflammatory bowel diseases (nonspecific chronic ulcerative colitis and Crohn's disease), and digestive functional disorders. Preclinical studies have shown significant efficacy of L. acidophilus LA85 in improving intestinal inflammation and barrier function in mouse models of ulcerative colitis. Human clinical evidence directly attributing benefit to L. acidophilus alone in IBD is limited; most relevant trials have used combination probiotic formulations.

6. Body Systems Associated with Lactobacillus acidophilus

• Gastrointestinal system: Primary site of action; implicated in modulation of gut microbiota composition, intestinal barrier integrity, diarrhea management, and IBS symptom relief.
• Immune system: Modulates innate and adaptive immune responses via interaction with dendritic cells, TLR2, NOD2, and induction of IL-10 and mucosal IgA.
• Genitourinary system: Contributes to maintenance of healthy vaginal microbiota and reduced susceptibility to bacterial vaginosis and vulvovaginal candidiasis.
• Cardiovascular/metabolic system: Proposed involvement in cholesterol modulation through BSH-mediated bile acid deconjugation; evidence primarily preclinical or from mixed-strain trials.
• Oral cavity: L. acidophilus was effective in reducing Streptococcus mutans levels in saliva.

7. Dosage Forms and Reported Dosages

L. acidophilus is commonly used at 1 × 10⁹–1 × 10¹⁰ CFU/day in supplements for general gut support.

The following dosages appear in the cited clinical literature:

• Acute gastroenteritis meta-analysis (pediatric): Effective when used at a daily dose of ≥ 10⁹ CFU. At dosages of more than 10⁹ CFU, moderate- to low-quality data showed reduction in diarrhea duration and frequency.
• Antibiotic-associated diarrhea (adult RCT, LA85): A total of 82 adult participants were randomized to receive either LA85 at 2 × 10⁹ CFU/day or a placebo containing 400 mg of maltodextrin for 14 days.
• IBS (NCFM dose-ranging study): Two different doses tested — 10¹⁰ CFU/day and 10⁹ CFU/day — of Lactobacillus acidophilus NCFM, with no statistically significant improvement reported for either dose in that trial.
• Vaginal health (La-14 combination): The La-14 strain was studied within a product containing 5 × 10⁹ CFU of La-14 and HN001 combined, with dosing varying from 1–2 capsules daily.

The primary elimination route is fecal passage; persistence is typically transient, often declining to baseline within days to weeks after discontinuation. This means continuous supplementation is generally required to maintain therapeutic levels.

8. Safety Considerations and Interactions

Regulatory Status

The European Qualified Presumption of Safety (QPS) and the American Generally Recognized as Safe (GRAS) concepts establish a generic risk assessment approach for biological agents. Both concepts are related but differ in approach: QPS provides an assessment tool for the EFSA, while GRAS lays the responsibility on the food business operator with FDA analyzing every case. Safety studies are performed before efficacy studies can take place, even for widely used probiotics that have a GRAS status. Specific strains such as DDS-1 have received FDA GRAS notices (e.g., GRN No. 871).

General Safety Profile

Probiotics have been used safely in foods and dairy products for over a hundred years. Although generally considered safe and well tolerated, the most common adverse effects are the GI symptoms of bloating and flatulence, which are typically mild and subside with continued use of the probiotic. The safety of heat-treated and lyophilized L. acidophilus LB has been demonstrated in two controlled clinical trials, with no adverse events being reported.

Risk in Immunocompromised Populations

Theoretical risks described in case reports, clinical trial results, and experimental models include systemic infections, deleterious metabolic activities, excessive immune stimulation in susceptible individuals, gene transfer, and gastrointestinal side effects. Despite their wide use and recognized safety, rare cases of serious infections in humans caused by lactic acid bacteria have been described in the literature, including bacteremia, endocarditis, pleuropneumonia, meningitis, and urinary tract infections. Epidemiological surveillance studies have, however, found no change in the rate of lactobacillemia in countries with increasing consumption of commercial probiotic Lactobacillus strains. No case of Lactobacillus isolated from the bloodstream was identified as being related to the probiotic strains.

L. acidophilus LB's administration is effective and safe as an adjuvant in the treatment of diarrhea, even in the presence of immunosuppression. A review of 57 clinical trials showed that the administration of probiotics and/or synbiotic organisms in immunocompromised adults — including those with HIV infection, critical illness, surgical conditions, and autoimmune disease — is safe. Nevertheless, safety issues such as the antimicrobial resistance of the lactobacilli and risks in certain groups — including immunocompromised patients and patients with short gut syndrome or undergoing cardiac surgery — warrant attention.

Antibiotic Interactions

Given that L. acidophilus is a live bacterium, concurrent antibiotic use can reduce or eliminate its viability in the gut. In clinical practice within the context of AAD prevention trials, the probiotic is typically administered at least 2 hours after an antibiotic dose to allow for partial survival; this timing was used in the LA85 trial discussed above. Antibiotic-associated diarrhea has incidence rates varying from 5% to 35%, primarily resulting from antibiotic-induced dysbiosis, characterized by disruptions in gut microbiota composition facilitating the proliferation of pathogenic or opportunistic microorganisms.

Strain-Level Specificity

Clinical evidence on strain-specific benefits remains inconsistent, highlighting that probiotic efficacy cannot be generalized across the entire species. The WHO/FAO working group has recommended that new probiotic strains be evaluated for safety by testing for antibiotic resistance, toxin production, and hemolytic potential, assessing metabolic activities such as D-lactate production and bile salt deconjugation, conducting human studies to evaluate side effects and post-market surveillance of commercial consumers, and, ideally, studying their use in immunocompromised animals to determine infectivity of the probiotic organism in this host type.

References

• The domestication of the probiotic bacterium Lactobacillus acidophilus — Scientific Reports / PMC
• NCBI Taxonomy Browser: Lactobacillus acidophilus (Taxonomy ID: 1579)
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• Lactobacillus acidophilus — Wikipedia
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