Digestive diseases are an important public health problem worldwide, affecting millions of people and imposing a huge medical and socio-economic burden. The digestive system, including the oral cavity, esophagus, stomach, intestines and liver, plays a central role in nutrient absorption, immune regulation and maintenance of metabolic homeostasis. In recent years, the incidence of IBD, irritable bowel syndrome, and gastrointestinal infections has continued to rise globally (Molodecky et al., 2012; Peery et al., 2022; Ricciardiello, 2022; Roy and Dhaneshwar, 2023), and there is an urgent need to explore new intervention strategies and therapeutic approaches.

A growing body of evidence suggests that the gut microbiota-a complex ecosystem of diverse microorganisms-plays a critical role in maintaining digestive and systemic health. An imbalance in the composition and function of the microbiota can lead to a variety of diseases including IBD, liver disease, metabolic syndrome and even neuropsychiatric disorders, with mechanisms of action involving immune regulation, epithelial barrier function, and the gut-brain axis (Cryan and Dinan, 2012; Rooks and Garrett, 2016; Fan and Pedersen, 2021). Therefore, strategies to regulate gut microbiota, especially the use of probiotics, have become a hot topic of current research in the prevention and treatment of digestive disorders. Probiotics are defined by the World Health Organization as “active microorganisms that are beneficial to the health of the host when ingested in adequate amounts” (Mu et al., 2018) and have been gradually applied in clinical interventions.

Among many probiotic candidates, L. johnsonii has drawn much attention. This is due to its robust colonization capacity, immunomodulatory potential, and diverse mechanisms of action. It was originally classified as L. acidophilus. L. johnsonii is a Gram-positive, non-bacteriophage-forming, partially anaerobic lactic acid bacterium. It is widely found in the gastrointestinal tract of both humans and animals (Yang et al., 2020). Like other Lactobacillus species such as L. acidophilus, L. johnsonii may contribute to host health in several ways. It can adhere to intestinal epithelial cells. It may enhance the mucosal barrier function. It also produces antimicrobial substances and modulates both innate and adaptive immunity (de Roos and Katan, 2000; Zhang et al., 2021). Specific strains of L. johnsonii have shown anti-inflammatory, antipathogenic, and metabolic-modulating properties. These traits suggest potential therapeutic value in conditions such as IBD, intestinal infections, liver diseases, and gut-brain axis disorders. Advances in histological techniques have deepened our understanding of its molecular mechanisms. Researchers have identified key proteins, such as GroEL and GAPDH, which are crucial in bacterium-host interactions (Xie et al., 2019). However, the functional differences and dose-dependent responses among strains suggest that precise screening and validation are still needed in probiotic development. A comprehensive 2024 review highlighted that probiotics-including specific Lactobacillus strains-modulate the gut-brain axis by regulating neuroinflammation, neurotransmitter production, and cognitive function in human trials involving mild cognitive impairment and dementia. This supports the potential of L. johnsonii and related probiotics in gut-brain disorders (Fekete et al., 2024).

This review systematically summarizes the current research progress of L. johnsonii in a variety of digestive diseases, covering its mechanism of action and potential clinical value in IBD, gastrointestinal infections, gastritis, obesity, hepatopathy, regulation of the gut-brain axis, gut microbiota dysbiosis, and colorectal cancer. We integrated representative results from animal experiments, cellular models and clinical studies (Tables 1–3), focusing on the analysis of its functional properties in regulating the intestinal barrier, metabolic intervention,maintenance of microbiota homeostasis and immune modulation. Currently, there are relatively few studies on the role of the specific strain L. johnsonii in digestive system diseases. This article provides readers with a comprehensive and focused update on the specific strain L. johnsonii, avoiding generalizations. This review not only describes the role of L. johnsonii within the gut but, more importantly, systematically and thoroughly explains how it influences distant organs such as the liver, brain, heart, and lungs through these axises. It systematically covers the research progress of L. johnsonii in almost all major digestive system-related diseases. This review also places significant emphasis on the differing effects of various L. johnsonii strains in specific disease models or clinical contexts. This review aims to provide theoretical support for the targeted use of L. johnsonii. It also lays a foundation for developing future precision probiotic interventions.

It is important to emphasize that the effects of probiotics are highly strain-specific. Even among different strains of L. johnsonii, there may be significant differences in their physiological properties, metabolites, host interaction mechanisms, and ultimate health effects. The results of the studies cited in this review are based on strain-specific experimental models or clinical observations unless otherwise stated, and the results cannot be simply extrapolated to other L. johnsonii strains or the species as a whole.

Changes in the gut microbiota can arise from shifts in bacterial community diversity or microbiota-host interactions, and these changes are directly linked to various diseases, particularly IBD, which encompasses Ulcerative Colitis (UC) and Crohn’s Disease (CD) (Hoarau et al., 2016). Numerous hypotheses have been put forward regarding the effects of probiotics on IBD: (1) Probiotics modulate the intestinal immune system through regulating the expression of pro-inflammatory cytokines (Liu et al., 2011). (2) Probiotics regulate the microbial balance of the gastrointestinal tract by inhibiting the growth of pathogens (Chen et al., 2013). (3) Probiotics enhance the function of the intestinal barrier by increasing the expression of tight junction proteins (Bai et al., 2022). Additionally, glycoconjugates from the Lactobacillus cell wall act as antigens that may serve as novel diagnostic biomarkers for IBD (Paściak et al., 2017). Biosynthesized poly-β-hydroxybutyrate (PHB) alleviates inflammation by regulating fucose residues to promote goblet cell differentiation and sulfomucin maturation, providing a favorable environment for L. johnsonii biofilm formation as seen in Figure 2 (Ma et al., 2022). The supernatant of L. johnsonii culture alleviated colitis and remodeled gut microbiota, with increased SCFA production inhibiting the MAPK signaling pathway and M1 macrophage polarization (Wu et al., 2023). L. johnsonii GLJ001 prevented dextran sulfate sodium (DSS)-induced colitis in mice by inhibiting M1 macrophage polarization via gut microbiota-SCFAs axis (Cai et al., 2025). Findings suggest that Butyrolactone-I (BTL-1) regulates intestinal flora, promotes the proliferation of L. johnsonii, safeguards the integrity of the intestinal barrier, increases the concentrations of butyric and propionic acids, and ultimately inhibits the activation of the MAPK signaling pathway in mice, thus alleviating IBD (Chen et al., 2025). In Muc2(−/−) mice, L. johnsonii demonstrates rapid growth, recovers to the initial population level and reduces the amount of Enterococcus faecalis (E. faecalis) (Makusheva et al., 2024). LJ-EVs can be directly internalized by intestinal epithelial cells and activate the Nrf2/HO-1 antioxidant signaling pathway, reducing endotoxin damage to cells and maintaining intestinal barrier homeostasis, which in turn alleviates the intestinal inflammation response (Li et al., 2024). There are fewer studies on LJ-EVs available. Future studies need to use sterile animal models or purified metabolite compartments to differentiate between the direct effects of Lactobacillus strains themselves and their metabolites or their potential synergistic effects. Additionally, research has revealed that β-Glucan ameliorates colitis via the L. johnsonii-indole-3-lactic acid (ILA)-aryl hydrocarbon receptor (AhR) axis (Zhang et al., 2024). Other studies have indicated that endoplasmic reticulum (ER) stress-related apoptosis is a crucial biological pathway in the pathophysiology of IBD (Cao et al., 2013; Ma et al., 2017). As shown in Figure 3. It has been demonstrated that L. johnsonii attenuated ER stress-related cell death (Zhang et al., 2021).

UC is a subtype of IBD characterized by persistent, nonspecific inflammation of the rectum and colon (Danese and Fiocchi, 2011; Ordás et al., 2012). Mounting evidence has revealed a significant correlation between L. johnsonii and the severity of UC (He et al., 2022). Research indicates that L. johnsonii activates resident macrophages, reprogramming them into CD206 + macrophages via the TLR1/2-the Signal transducer and activator of Transcription3 (STAT3) signaling pathway. This activation elicits the release of IL-10, effectively alleviating experimental colitis (Jia et al., 2022). The product ID-JPL934 comprises L. johnsonii IDCC9203 (isolated from infant feces), which demonstrated the ability to the model for UC, including the constriction of the length of the colon, immune cell infiltration in the mucosa and submucosa, severe crypt damage, and loss of goblet and epithelial cells as observed in histological analysis (Je et al., 2018).

CD is another IBD that has seen a significant increase in incidence worldwide in recent years (Ng et al., 2017; Shouval and Rufo, 2017). Unlike UC, CD can affect the entire digestive tract, with transmural and segmental inflammation most commonly found in the terminal ileum and colon (Torres et al., 2017). Evidence suggests that the pathogenesis of CD is a result of gut inflammation caused by a combination of genetic and microbial factors, leading to abnormal immune regulation in the host (Ramos and Papadakis, 2019; Roda et al., 2020). Existing research suggests that the impact of L. johnsonii in the management of CD appears to be rather limited. The elemental diet (ED), widely utilized as an enteral nutritional intervention for CD, leads to a decrease in the population of L. johnsonii. This reduction is accompanied by a decline in the quantity and diversity of the intestinal microbiota, as well as a decrease in proinflammatory cytokines. Such changes are likely a consequence of alterations in the composition of lactic acid bacteria (Kajiura et al., 2009). A randomized, double-blind, placebo-controlled study, which spanned over 6 months, concluded that L. johnsonii LA1 was not significantly effective, if at all, in preventing endoscopic recurrence of CD (Marteau et al., 2006). Another multicenter randomized-controlled clinical trial had the similar result, which failed to prevent early endoscopic recurrence 12 weeks after ileo-colorectal resection (Van Gossum et al., 2007). The reasons for the ineffectiveness of L. johnsonii LA1 need to be further investigated. The potential influence of inter-individual differences in the patient’s gut microbiota may be a contributing factor.

The discrepancy between clinical and basic research findings may be influenced by multiple factors. First, strain-level variability should not be overlooked. Within the L. johnsonii species, substantial genomic diversity exists, leading to significant differences among strains in terms of metabolite production, colonization capacity, and immunomodulatory properties. Therefore, the anti-inflammatory effects demonstrated by certain strains in animal models or in vitro experiments may not be directly applicable to all clinical settings (Arzola-Martínez et al., 2024). Second, host-related factors also play a critical role. Individual differences among CD patients, including genetic background, gut microbiota composition, baseline inflammation levels, and postoperative recovery status, can affect the colonization efficiency and functional expression of L. johnsonii, thereby contributing to inconsistent intervention outcomes. Moreover, limitations in the design of existing clinical trials—such as short intervention durations, limited follow-up periods, and the lack of standardized dosages and delivery methods—may further obscure the potential long-term benefits of L. johnsonii.

In this context, future research should focus on precise strain selection, taking into account host-specific characteristics, and optimizing clinical trial protocols. Such efforts are essential to comprehensively evaluate the true therapeutic potential of L. johnsonii in CD management and to elucidate the fundamental reasons underlying the gap between mechanistic studies and therapeutic reality.

Psoriasis and IBD exhibit resemblances in terms of their commensal microbial communities and immune mechanisms. A prior investigation demonstrated that in the imiquimod (IMQ) mouse model (van der Fits et al., 2009; Van Belle et al., 2012; Terhorst et al., 2015), which is a murine model for psoriasis, the gut microbiome undergoes perturbations with reduced L. johnsonii and Lactobacillus reuteri (L. reuteri) populations (Kiyohara et al., 2019). This finding implies a potential connection between the skin microbiota and the gut microbiota in the context of psoriasis.

In summary, L. johnsonii exerts multifaceted regulatory effects on intestinal homeostasis in IBD, particularly by reshaping gut microbiota, strengthening barrier function, modulating immune responses, and alleviating inflammation through SCFA production and signaling pathway regulation. Despite promising results in UC models, its efficacy in Crohn’s disease and therapeutic reality s remains inconclusive. Future studies should prioritize clarifying strain-specific mechanisms, exploring microbial metabolite-host interactions, and investigating the role of L. johnsonii in extraintestinal diseases linked to gut dysbiosis, such as psoriasis.

H. pylori is a Gram-negative pathogen with spiral motility and ability to colonize acidic stomach. Chronic infection causes diseases, including chronic active gastritis, chronic atrophic gastritis, peptic ulcer and cancer. Previous studies have indicated that probiotics may hold potential in the treatment of H. pylori infection (Malfertheiner et al., 2002). L. johnsonii intake has a weak but favorable effect on associated gastritis (Pantoflickova et al., 2003), like L. johnsonii La1 strain reducing colonization in children (Felley et al., 2001; Cruchet et al., 2003; Gotteland et al., 2008).

Regarding the mechanism of L. johnsonii inhibition of H. pylori associated gastritis, the current study did the following. As mentioned earlier, the surface GroEL protein of L. johnsonii La1 has been identified to possess activities contributing to its probiotic characteristics. These activities include attachment to mucus and epithelial cells, stimulation of cytokine secretion from macrophages and epithelial cells, and the capacity to mediate the aggregation of the gastric pathogen H. pylori. L. johnsonii La1 GroEL binds to mucins and intestinal HT29 cells in a pH-dependent manner: while a strong binding capacity was observed at pH 5.0, no binding occurred at pH 7.2. The recombinant GroEL (rGroEL) protein of L. johnsonii La1 can induce the aggregation of H. pylori (Bergonzelli et al., 2006). An acidic pH environment induces stress-sensitive GroEL expression and increases L. johnsonii La1 death (Bergonzelli et al., 2006). In the early infection stages of H. pylori, L. johnsonii La1 can reduce gastritis reducing macrophage inflammatory protein 2 (MIP-2) and keratinocyte-derived cytokine (KC) in serum and mucosa. Neutralized L. johnsonii La1 spent culture supernatant reduces IL-8 secretion by human adenocarcinoma AGS cells, which may be through a reduction in pro-inflammatory chemotactic signals that recruit lymphocytes and neutrophils in the lamina propria (Sgouras et al., 2005). Both live and lyophilised strains of L. johnsonii No. 1088 (HK-LJ88) can inhibit H. pylori growth in mice, not through co-aggregation but an unknown mechanism involving cell surface molecules (Aiba et al., 2015; Aiba et al., 2017). Additionally, HK-LJ88 can inhibit gastric acid secretion by reducing gastrin-positive cells (Aiba et al., 2015). The GroEL protein of L. johnsonii La1 is a core effector for its gastric colonization and anti-Hp, which is distinct from other strains of Enterobacteriaceae such as L531 and BS15 in terms of molecular targeting. For example, LJ-EVs are important in activating the Nrf2/HO-1 antioxidant pathway induction, and M2 macrophage polarization. L531 alters the composition of the intestinal microbiota and the production of SCFA, which attenuates intestinal infections. However, the specific adhesion mechanism with intestinal epithelial cells has not been clearly elucidated. BS15, on the other hand, possesses major functions in regulating metabolism and strengthening the intestinal mucosal barrier. Future studies could focus on their differences in molecular targets or mechanisms of action.

Studies also showed that L. johnsonii 456 has higher viability at lower pH compared to other strains (Davoren et al., 2019), and proton pump inhibitors (PPIs) can reduce L. johnsonii and exacerbate indomethacin-induced small intestinal damage (Nadatani et al., 2019). Lactic acid from L. johnsonii plays a protective role in NSAID-induced small bowel injury. The discrepancy observed in these research outcomes can be ascribed to a diverse range of factors. For example, significant differences exist in assay results when examining the gut microbiota of mice versus humans. Additionally, variations in the bacterial homeostasis of the gastrointestinal mucosa among different individuals contribute to these discrepancies. These factors highlight the urgent need for further in-depth exploration, especially in identifying elements that foster the survival of gut microbiota and their adhesion to the gastrointestinal tract.

Based on the above, L. johnsonii exhibits strain-specific potential in mitigating H. pylori-induced gastritis by modulating host immune responses, interfering with pathogen adhesion, and influencing gastric environment via factors like GroEL protein and lactic acid production. While strains such as L. johnsonii La1 and No. 1088 have shown efficacy in reducing H. pylori colonization and associated inflammation, variations in outcomes across studies underscore the complexity of host–microbiota–pathogen interactions. Future research should focus on elucidating the molecular pathways underpinning these probiotic effects, optimizing strain viability under gastric conditions, and identifying host-specific factors influencing probiotic colonization and therapeutic efficacy. Personalized approaches integrating microbial and host biomarkers may ultimately improve probiotic strategies against H. pylori.

Obesity and related metabolic disorders result from excessive caloric intake and insufficient physical activity, leading to fat accumulation and various diseases (Xu et al., 2003). Evidence shows probiotics, including Lactobacillus, help restore metabolic and immune function (Dahiya et al., 2017; Park et al., 2018, 2019). L. johnsonii, from human and animal intestines, has strains with probiotic properties (Fukushima et al., 2007; Buhnik-Rosenblau et al., 2012; Fonseca et al., 2017; Zheng et al., 2020). Its progress in obesity metabolism and fatty liver disease is as follows.

Lactobacillus johnsonii has anti-obesity and cholesterol-lowering effects. L. johnsonii JNU3402 (LJ3402), from Korean infant feces, is bile and acid resistant. In high-fat diet mice, non-viable LJ3402 was observed to reduce liver weight, as well as epididymal white adipose tissue (WAT), regulate triglyceride levels, and slightly improve insulin resistance. The anti - obesity effect of LJ3402 is mediated via the PPARγ pathway. This pathway not only enhances mitochondrial function within WAT but also promotes thermogenesis (Yang et al., 2020). Phycobiliproteins (derived from arthrospira platensis) bioactive peptide extracts (PPE) can increase L. johnsonii abundance and is a potential supplement for obesity (Liu et al., 2022). Another study linked hypercholesterolemia to liver cholesterol metabolism. L. johnsonii BFE6154 exerts its cholesterol - lowering effect by downregulating the expression of the Niemann-Pick C1-like 1 (NPC1L1) gene. It achieves this by activating the liver X receptor (LXR) in liver cells, thereby reducing cholesterol uptake. Furthermore, the metabolite of L. johnsonii BFE6154 stimulates the expression of the low density lipoprotein receptor (LDLR) gene in hepatocytes, facilitating enhanced cholesterol clearance. In the intestine, L. johnsonii BFE6154 upregulates the ABCG5 gene while downregulating the ABCG8 and NPC1L1 genes, effectively curbing intestinal cholesterol absorption. These findings have substantially enhanced our understanding of the complex cholesterol-lowering mechanisms of L. johnsonii (Yoon et al., 2023).

The high degree of co-morbidity between diabetes mellitus and MAFLD and their common pathophysiologic basis (insulin resistance, chronic low-grade inflammation, intestinal flora dysbiosis, intestinal barrier damage, and gut-hepatic axis disturbances). This overlapping of multiple pathologies creates more complex stresses on host metabolism and the intestinal microenvironment, challenging traditional monotherapies. L. johnsonii has shown potential in modulating obesity and related metabolic disorders such as insulin resistance, dyslipidemia (e.g., strain JNU3402, BFE6154). These metabolic benefits, together with its potential hepatoprotective effects, make it one of the candidate probiotics for exploring interventions in the obesity-diabetes-fatty liver “metabolic co-morbidity syndrome.” Strains like L. johnsonii with potential to modulate metabolism and the gut environment serve as potential adjunctive intervention strategies. Future studies need to deeply explore their effects and mechanisms in the superimposed state of multiple metabolic disorders.

In a word, L. johnsonii exhibits notable potential in combating obesity and related metabolic disorders through multiple mechanisms. Specific strains such as LJ3402 demonstrate anti-obesity effects by enhancing mitochondrial function and promoting thermogenesis via the PPARγ pathway, while BFE6154 exerts cholesterol-lowering activity by modulating key hepatic and intestinal genes involved in lipid absorption and metabolism. Additionally, dietary interventions like phycobiliprotein-derived peptides may further augment L. johnsonii abundance, offering a synergistic approach to metabolic regulation. These findings highlight the multifaceted metabolic benefits of L. johnsonii, warranting further investigation into its clinical efficacy and application in personalized metabolic therapies.

Lactobacillus johnsonii plays a critical role in gastrointestinal (GI) health through immunomodulatory mechanisms, reinforcement of intestinal barrier functionality, and attenuation of inflammatory responses. Although the specific effects vary depending on the strain and application context, this review reveals that the potential common mechanisms underlying the probiotic functions of L. johnsonii primarily include: regulating the composition and function of the gut microbiota (e.g., increasing beneficial bacteria and inhibiting pathogenic bacteria); enhancing or repairing the intestinal barrier (e.g., promoting the expression of tight junction proteins and increasing mucus secretion); modulating host immune responses (e.g., regulating cytokine secretion and influencing immune cell differentiation); producing bioactive metabolites (SCFAs, ILA, PCA, etc.); and mediating distant organ effects. However, translating preclinical and clinical findings into robust applications faces significant hurdles, including strain-specific variability in probiotic efficacy (e.g., divergent outcomes between L. johnsonii La1 and BS15 in IBD management), inconsistent clinical trial results (such as the failure of L. johnsonii La1 to prevent CD recurrence), and fragmented regulatory frameworks for validating health claims. These challenges underscore the need for strain-specific characterization, precised strain identification and functional validation, personalized probiotic strategies aligned with individual microbiota profiles, and harmonized safety and efficacy standards across jurisdictions. In summary, despite significant differences in the actions of different strains of L. johnsonii, the available research strongly suggests that the strain as a whole holds core effects on great potential to improve digestive health and associated systemic diseases through the multiple mechanistic modules mentioned above (flora modulation, barrier repair, immunomodulation, metabolite production, other organs) Potential. The positive effects (e.g., anti-infective, anti-inflammatory, metabolic regulation, neuroprotection) demonstrated by many strains in specific models or clinical situations provide an important basis and direction for further research and development of this strain.

Despite established anti-inflammatory mechanisms mediated through TLR/STAT3 signaling and ER stress modulation, critical gaps persist in elucidating the bioactive metabolites (e.g., propionic acid, bacteriocins) and host–microbe interactions underlying L. johnsonii’s effects. Current research is further constrained by overreliance on animal models and small-scale human trials, which may fail to recapitulate human pathophysiology or account for microbiome heterogeneity. Further, the potential impact of host genetic factors (e.g., polymorphisms in NOD2, TLR4) on strain efficacy remains worth exploring. In case the results of the study may be biased. Additionally, the interplay between L. johnsonii and comorbid conditions, such as metabolic disorders or mental health issues, remains underexplored, necessitating advanced multi-omics approaches to identify predictive biomarkers.

Lactobacillus johnsonii also has an interaction network with other major symbiotic bacteria, such as Bifidobacterium or Bifidobacterium. Charlet et al. (2020) found that L. johnsonii can co-secrete chitinase and mannosidase with Bacteroides thetaiotaomicron to degrade fungal cell walls. This significantly inhibits the overgrowth of Candida species and reduces the abundance of pathogenic bacteria such as E. coli and Enterococcus, thereby alleviating colitis symptoms in mice (Charlet et al., 2020). In addition to its local effects, L. johnsonii can also influence systemic diseases through microbiota remodeling. For example, in a rat model of AMI, L. johnsonii can increase the abundance of Muribaculaceae and Lactobacillus while decreasing the levels of potential pathogens such as Romboutsia and Clostridia, thereby improving cardiac function and demonstrating its potential to modulate the function of distal organs through the “gut-heart axis” (Zhong et al., 2023). In terms of competitive colonization, L. johnsonii can bind tightly to host epithelial cells via surface proteins, which may affect the ecological niches occupied by other microorganisms. The surface “moonlighting protein” GAPDH of L. johnsonii can bind to the tight junction protein JAM-2 of intestinal epithelial cells, thereby enhancing intestinal barrier function and providing an advantage for its stable colonization (Bai et al., 2022). In addition, this strain exhibits potent antimicrobial capabilities, inhibiting a variety of pathogenic microorganisms, including H.pylori, E. coli, Salmonella, and Clostridium difficile, thereby further altering the gut microbiota structure (Aiba et al., 2015).

Future research priorities include large-scale, double-blind randomized controlled trials (RCTs) to evaluate strain- and disease-specific efficacy in IBD subtypes, H. pylori eradication, and metabolic syndrome. Meanwhile, future therapeutic reality of L. johnsonii necessitate meticulous strain selection, as distinct strains (e.g., L. johnsonii La1, L531, BS15) exhibit divergent therapeutic effects across digestive diseases, underscoring the importance of strain-specific mechanistic studies and rigorous clinical validation to optimize probiotic efficacy and safety. Mechanistic studies should integrate genomics, proteomics, and metabolomics to map strain-specific pathways, such as GroEL-mediated pathogen aggregation or GAPDH-JAM-2 interactions in epithelial barrier repair. Concurrent efforts to optimize industrial-scale production through culture condition refinement or genetic engineering could enhance probiotic viability and functionality. Safety assessments in vulnerable populations (e.g., immunocompromised individuals, neonates) are imperative to address risks like horizontal gene transfer or opportunistic infections. Finally, interdisciplinary collaboration is essential to develop standardized guidelines for probiotic use, validate functional food formulations, and establish regulatory pathways that balance innovation with public health safeguards. By addressing these challenges, L. johnsonii may transition from a promising probiotic to a cornerstone of precision medicine in gastrointestinal and systemic health management.

In conclusion, L. johnsonii emerges as a clinically significant probiotic strain that demonstrates critical efficacy in human health maintenance, particularly in the context of gastrointestinal disorder management, while exhibiting substantial translational potential for therapeutic applications in digestive tract pathologies.

Further research should prioritize elucidating strain-dependent molecular pathways and conducting large-scale trials to establish tailored therapeutic strategies for targeted disease interventions.