Lactobacillus rhamnosus GR-1: Roles in the Human Microbiome

Lactobacillus rhamnosus GR-1 is a well-studied bacterial strain recognized for its role in human health, particularly within the microbiome. It has been extensively researched for its benefits in maintaining urogenital and gut health, with applications in probiotics and therapeutic interventions.

Classification And Taxonomy

Lactobacillus rhamnosus GR-1 belongs to the Lactobacillaceae family, a group of lactic acid bacteria involved in fermentation and host-associated symbiosis. The genus Lactobacillus was recently reclassified, with Lactobacillus rhamnosus now placed in the Lacticaseibacillus genus. Despite this change, GR-1 is still widely referred to under its traditional nomenclature in clinical and commercial contexts.

The species Lacticaseibacillus rhamnosus is closely related to Lacticaseibacillus casei, but genomic studies have identified distinct markers differentiating them, particularly in carbohydrate metabolism and stress tolerance. These differences enable L. rhamnosus to thrive in diverse environments, including the gastrointestinal and urogenital tracts. GR-1 has been extensively studied for its probiotic properties, distinguishing it from other strains.

Strain-level classification is crucial in probiotic research, as genetic variations influence functional properties. Whole-genome sequencing and multilocus sequence typing (MLST) confirm GR-1’s unique genetic profile compared to strains like L. rhamnosus GG. These analyses reveal adaptations linked to adhesion, biofilm formation, and antimicrobial compound production, enhancing its persistence in the host microbiome.

Distinctive Growth Conditions

Lactobacillus rhamnosus GR-1 thrives in diverse environments due to its adaptability to pH levels, nutrient availability, and oxygen conditions. It grows optimally at 35–37°C, aligning with the human body’s internal environment, but can tolerate lower temperatures, allowing it to persist in food products and probiotic formulations. Its facultative anaerobic nature enables survival in both oxygen-rich and oxygen-limited conditions, making it well-suited for colonization in the gastrointestinal and urogenital tracts.

GR-1 can survive in highly acidic conditions down to pH 3, enabling it to withstand gastric transit. This acid resistance is facilitated by the F0F1-ATPase proton pump, which expels protons to maintain pH homeostasis, and by exopolysaccharide production, which forms a protective barrier. These mechanisms aid survival in the stomach and acidic microenvironments such as the vaginal tract.

The strain efficiently metabolizes glucose, lactose, maltose, and prebiotic fibers like inulin and fructooligosaccharides. This metabolic flexibility, supported by a well-developed carbohydrate transport system, allows it to interact with dietary components and influence gut microbiota composition.

GR-1 also exhibits high bile salt tolerance, a key trait for survival in the small intestine. It can endure bile concentrations up to 0.3%, aided by bile salt hydrolases (BSHs), which detoxify bile acids. This resistance enhances bacterial survival and influences host lipid metabolism, reinforcing its suitability for oral probiotic formulations.

Genome Features

The genome of Lactobacillus rhamnosus GR-1, approximately 2.9 megabases (Mb) with a GC content of 46.7%, encodes genes that support survival in host-associated environments. Comparative genomic analyses identify unique gene clusters linked to adhesion, biofilm formation, and stress resistance, which contribute to its persistence in the human microbiome.

GR-1 possesses surface adhesion proteins, including mucus-binding proteins and fibronectin-binding adhesins, enhancing its ability to attach to host tissues. It also carries genes encoding SpaCBA-type pili, which aid biofilm formation and competitive exclusion of pathogens, supporting long-term colonization.

The strain’s genome includes stress response mechanisms, such as heat shock proteins and oxidative stress defenses, ensuring survival under environmental fluctuations. Genes involved in DNA repair enhance resilience in inflammatory or oxygen-variable environments, supporting its viability during transit through the digestive system and within the microbiome.

Common Dietary Sources

Lactobacillus rhamnosus GR-1 is primarily found in probiotic supplements and functional foods rather than naturally occurring in most fermented foods. Commercial probiotic formulations, including capsules, powders, and liquid suspensions, commonly contain GR-1, delivering between 1 to 10 billion colony-forming units (CFU) per serving.

While traditional fermented foods like yogurt, kefir, and certain cheeses contain various lactic acid bacteria, GR-1 is generally not present unless specifically added during fermentation. Some dairy-based probiotics incorporate it to enhance microbial diversity. Non-dairy alternatives, including plant-based probiotic beverages and fortified fermented foods, also serve as delivery vehicles for GR-1, making it accessible to individuals with dietary restrictions.

Interactions In The Microbiome

Lactobacillus rhamnosus GR-1 influences microbial communities in the gastrointestinal and urogenital tracts. By producing lactic acid, it helps maintain an acidic environment that inhibits pathogens like Escherichia coli and Gardnerella vaginalis. This acidification is particularly beneficial in the vaginal microbiome, where GR-1 supports a balanced microbial composition. Additionally, it secretes bacteriocins, antimicrobial peptides that selectively target pathogens while preserving beneficial microbes.

GR-1 also interacts with commensal bacteria such as Bifidobacterium species, which ferment dietary fibers into short-chain fatty acids (SCFAs) like butyrate. These metabolites support gut health by providing energy to colonocytes and regulating inflammation. GR-1’s biofilm-forming ability further influences microbial dynamics by preventing pathogen adhesion and fostering a stable niche for beneficial bacteria, contributing to microbiome resilience.

Methods Of Detection In Research

Identifying Lactobacillus rhamnosus GR-1 requires precise detection methods to distinguish it from related strains. Culture-based techniques use selective media like de Man, Rogosa, and Sharpe (MRS) agar, which supports lactic acid bacteria growth while inhibiting non-lactobacilli species. However, culture methods alone are insufficient for strain-level identification, necessitating molecular approaches such as polymerase chain reaction (PCR) and quantitative PCR (qPCR), which target strain-specific genetic markers.

Advanced genomic methods, including whole-genome sequencing (WGS) and metagenomics, provide deeper insights into GR-1’s presence and function. WGS differentiates it from other L. rhamnosus strains by identifying unique single nucleotide polymorphisms (SNPs) and strain-specific genes. Metagenomic sequencing allows researchers to study GR-1’s interactions with other microbes by analyzing microbial DNA from complex biological samples. Fluorescence in situ hybridization (FISH) further aids visualization within host tissues, offering spatial context for its colonization patterns.

Variation Among Related Strains

While Lactobacillus rhamnosus GR-1 shares genomic traits with other L. rhamnosus strains, it exhibits distinct genetic and functional differences that influence its probiotic properties. One of the most well-characterized comparisons is with L. rhamnosus GG, another widely studied probiotic strain. Despite their genetic similarity, GG is primarily associated with gastrointestinal benefits, while GR-1 is extensively researched for urogenital health. These differences stem from variations in adhesion-related genes, with GR-1 possessing unique surface proteins that enhance colonization in the vaginal and urinary tracts.

GR-1 also demonstrates superior survival in acidic environments and a broader capacity for carbohydrate metabolism, allowing it to persist in niches where other L. rhamnosus strains may struggle. Additionally, variations in bacteriocin production contribute to strain-specific antimicrobial properties, with GR-1 exhibiting enhanced inhibitory effects against uropathogens. These distinctions highlight the importance of strain-level classification in probiotic research, as even closely related strains can have markedly different physiological behaviors and clinical applications.