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Bifidobacterium longum

Bifidobacterium longum is a Gram-positive, , non-spore-forming, rod-shaped bacterium belonging to the phylum Actinobacteria and the genus Bifidobacterium, characterized by its often branched, Y-shaped morphology and high G+C content of approximately 60%. It is a prominent commensal member of the , one of the first microbes to colonize the gut shortly after birth—particularly in breastfed infants where it can comprise up to 90% of the fecal —and persists at lower levels (3–6%) into adulthood. This species plays a pivotal role in early microbial succession, metabolizing complex carbohydrates such as oligosaccharides via specialized transport systems and producing like and , which support gut and inhibit pathogens. Taxonomically, B. longum encompasses four subspecies—B. longum subsp. longum, infantis, suis, and suillum—each adapted to specific hosts or niches, with B. longum subsp. infantis notably specialized for infant colonization through its ability to degrade human milk glycans. The bacterium's genome, typically ranging from 2.2 to 2.8 Mb with 1,800–2,600 genes, exhibits high genetic diversity that enables strain-specific adaptations, including adhesion mechanisms like type IV pili for intestinal colonization and persistence for months or years in the host. Found not only in human feces and intestines but also in animal sources (e.g., pig and calf feces for subsp. suis and suillum) and environmental samples like water, B. longum demonstrates broad ecological versatility while being recognized as generally safe (GRAS) by regulatory bodies such as the FDA and EFSA. As a widely used , B. longum strains confer numerous health benefits, including modulation of the composition, enhancement of intestinal barrier integrity, and reduction of through production and interactions. Clinical and preclinical studies highlight its efficacy in alleviating conditions such as (IBS), (IBD), , and even stress-related disorders via the gut-brain axis, with specific strains like B. longum 1714 shown to lower levels and improve mood in humans. Additionally, it competitively excludes pathogens, reduces the risk of in infants, and supports metabolic health by mitigating and lipid accumulation in high-fat diet models. These properties underscore B. longum's significance in both natural gut ecology and therapeutic applications, with ongoing research exploring its genomic and functional diversity for targeted interventions.

Taxonomy

Classification

Bifidobacterium longum is classified within the genus , which belongs to the Actinobacteria, class Actinobacteria, order Bifidobacteriales, and family Bifidobacteriaceae. This placement reflects its Gram-positive, non-spore-forming, nature and its phylogenetic position as one of the earliest diverging lineages in the Actinobacteria . In 2002, the distinct species Bifidobacterium infantis and Bifidobacterium suis were unified with B. longum into a single species based on their high genetic similarity, specifically greater than 97% sequence identity in the 16S rRNA gene. This taxonomic revision, proposed by Sakata et al., addressed the close phylogenetic relationships revealed by molecular analyses and emphasized the shared phenotypic traits among these taxa. In 2008, the three biotypes (infantis, longum, and suis) were formally reclassified as subspecies: B. longum subsp. longum, B. longum subsp. infantis, and B. longum subsp. suis. A fourth subspecies, B. longum subsp. suillum, was described in 2015 based on and analyses, distinguishing it from subsp. suis by genomic and phenotypic differences. These maintain distinct ecological niches despite their genetic consolidation. Strain identification within B. longum relies on PCR-based techniques targeting species-specific genetic markers, such as 16S rRNA or other conserved genes, for rapid detection and differentiation. More precise delineation uses whole-genome sequencing, applying thresholds like greater than 95% average nucleotide identity (ANI) to confirm strains belong to the same species or subspecies.

Subspecies and Strains

Bifidobacterium longum is divided into four recognized based on genomic, phenotypic, and ecological distinctions: B. longum subsp. longum (type NCC 2705), commonly isolated from the gut and serving as a reference for the ; B. longum subsp. infantis, specialized for utilizing oligosaccharides, enabling it to dominate the gut through efficient of complex glycans like human milk oligosaccharides; B. longum subsp. suis, primarily found in the porcine intestine, reflecting host-specific adaptations in utilization and environmental persistence; and B. longum subsp. suillum (type DSM 28597), mainly isolated from pig feces but also detected in gut samples, characterized by differences in multilocus sequence profiles. The exhibits substantial diversity, with over 2,000 genomes sequenced to date, revealing intraspecies variations particularly in genes related to utilization, such as hydrolases and transporters that influence niche adaptation in the gut. These variations contribute to functional heterogeneity, allowing strains to exploit diverse dietary substrates and interact differently with host . In 2025, a novel , B. longum subsp. , was proposed in a based on analysis of 435 genomes, highlighting genomic divergences (e.g., average identity thresholds) and phenotypic traits like predominantly rod-shaped morphology in chains with visible septa, distinguishing it from the typical Y-shaped forms of other . Strain distinction within B. longum relies on (MLST), which sequences multiple housekeeping genes to resolve phylogenetic relationships, and analyses that delineate core (ubiquitous) genes from accessory (variable) elements, often linked to adaptive traits like glycan metabolism.

Ecology

Habitats

Bifidobacterium longum thrives in environments, with its primary natural habitats including the gastrointestinal tracts of humans and certain . The subspecies B. longum subsp. suis (and the related subsp. suillum, isolated from pig feces) is specifically adapted to porcine gut conditions, isolated from the intestines and feces of . Beyond humans and pigs, related Bifidobacterium species have been detected in the digestive tracts of other such as , sheep, goats, horses, rabbits, chickens, geese, and pigeons, though B. longum itself is primarily host-specific to humans (subsp. longum and infantis) and pigs. Additionally, B. longum is found in fermented products and traditional ferments, such as milk-based foods, where it participates in processes. Isolations have also been reported from environmental sources like , indicating a broader ecological distribution outside host-associated niches. These non-animal habitats underscore the bacterium's versatility in oxygen-limited, nutrient-rich settings derived from decomposition. B. longum exhibits notable environmental tolerance that supports its persistence across these diverse niches, including survival in low-pH conditions akin to and bile-rich environments, facilitated by a robust and mechanisms such as efflux pumps and exopolysaccharide production. It prefers growth at approximately 37°C under microaerophilic to strictly conditions, with optimal around 6.5–7.0, though it remains viable at pH 3.5–4.0 through acid tolerance responses involving proton extrusion and cytoplasmic buffering. These adaptations enable of varied sites. In terms of distribution, B. longum is but achieves its highest abundance in mammalian guts, reflecting influences from host availability and environmental factors. General trends in suggest lower overall bifidobacterial diversity in industrialized populations compared to rural ones, potentially linked to dietary and exposure differences, though specific data for B. longum in adults requires further study.

Role in Microbiota

Bifidobacterium longum is a prominent early colonizer of the human , particularly in breastfed infants where it can constitute up to 90% of the fecal , facilitating the establishment of a healthy dominated by bifidobacteria. This dominance is attributed to its specialized ability to metabolize human milk oligosaccharides, promoting selective growth in the neonatal environment. As individuals age, B. longum abundance declines significantly, stabilizing at 3-6% of the adult , with further reductions observed in the elderly. However, its persistence is influenced by diet; populations consuming non-Western diets rich in plant-derived fibers, such as arabinoxylans, exhibit higher and more sustained levels of B. longum compared to those on diets. The ability of B. longum to colonize the relies on sophisticated mechanisms, including the production of fimbriae-like structures such as Tad pili, exopolysaccharides that enhance mucus interactions, and specific mucus-binding proteins that mediate attachment to host glycans. These adhesins enable B. longum to bind effectively to the layer and epithelial cells, supporting its transient or persistent residency in the gut without causing displacement of the native . Within the gut ecosystem, B. longum engages in competitive and interactions that shape microbial . It inhibits pathogens through the production of , including , which lowers the intestinal pH and creates an unfavorable environment for harmful bacteria. Additionally, B. longum participates in cross-feeding networks, generating that serves as a for butyrate-producing bacteria like prausnitzii, thereby promoting overall microbial diversity and metabolic stability. Alterations in B. longum abundance are associated with gut in various conditions, where its levels are notably reduced in individuals with and (IBD), contributing to impaired barrier function and inflammation. Studies on fecal microbiota transplantation (FMT) demonstrate its potential to restore B. longum populations in dysbiotic states, such as active , leading to improved microbial balance and disease remission.

Physiology

Morphology and Growth

Bifidobacterium longum is a Gram-positive, branched rod-shaped , typically measuring 1-5 μm in length, with cells often appearing as short, curved, club-shaped, or bifurcated Y- or V-shaped forms due to branching during growth. It is non-motile, non-spore-forming, and catalase-negative, characteristics that distinguish it from many other gut-associated and contribute to its adaptation in environments. The bacterium exhibits slow growth under optimal conditions, with a doubling time of approximately 1-2 hours, reflecting its specialized physiology as a strict anaerobe or microaerophilic organism. Growth is favored in anaerobic or microaerophilic atmospheres at temperatures of 37-40°C and pH levels between 6.5 and 7.0, conditions that mimic the human intestinal milieu and support its proliferation without excessive oxidative stress. These requirements underscore B. longum's dependence on oxygen-limited niches for viability and metabolic efficiency. The cell wall of B. longum features a high G+C content of around 60%, which enhances genomic stability and influences cell envelope rigidity. It is composed of layers anchored with teichoic acids, including ribitol and types, along with surface-associated proteins and that provide structural protection against environmental stressors such as low and bile salts. To assess cell viability in survival studies, particularly for probiotic applications, propidium monoazide (PMAxx)-qPCR has emerged as a reliable 2024 method, enabling differentiation between live and dead B. longum cells by penetrating compromised membranes and inhibiting PCR amplification of DNA from non-viable bacteria. This technique offers higher sensitivity and specificity compared to traditional culture-based assays, facilitating accurate quantification in complex matrices like the gut or fermented foods.

Metabolism

_Bifidobacterium longum primarily relies on a fermentative , utilizing the characteristic bifid shunt pathway, also known as the fructose-6-phosphate phosphoketolase pathway, for the of hexoses. This unique fermentative process via the bifid shunt pathway produces and in a molar ratio of 2:3 (:), with a net yield of approximately 1 + 1.5 per glucose and 2.5 ATP molecules per glucose molecule metabolized. The overall reaction for two glucose molecules can be summarized as: $2 \text{ Glucose} \rightarrow 2 \text{ Lactic acid} + 3 \text{ Acetic acid} + 5 \text{ ATP} This pathway distinguishes B. longum from other lactic acid bacteria by bypassing parts of the traditional Embden-Meyerhof-Parnas glycolysis, allowing efficient energy extraction under anaerobic conditions typical of the gut environment. B. longum demonstrates versatile carbohydrate utilization, supported by 19 predicted sugar permeases for the uptake of diverse monosaccharides and oligosaccharides, and more than 40 glycosyl hydrolases that cleave complex glycans. These enzymes enable the breakdown of substrates such as human milk oligosaccharides (HMOs), galactomannan, and arabinoxylans, facilitating adaptation to varied dietary fibers in the human gut. The subspecies B. longum subsp. infantis shows particular specialization in HMO metabolism, featuring dedicated gene clusters with multiple fucosidases, sialidases, and ABC transporters for intracellular processing of these prebiotic structures abundant in breast milk. Beyond carbohydrates, B. longum engages in catabolism through enzymes including serine dehydratase, aldolase, and 2-hydroxyacid homologs, allowing of peptides and free as supplementary energy sources. It also possesses hydrolase activity, which deconjugates - and glycine-linked salts like taurocholate, aiding survival in the bile-rich . Approximately 8-12% of the B. longum is devoted to catabolic functions, underscoring its scavenger-like metabolic strategy for exploiting host-derived and dietary nutrients. The main byproducts of B. longum metabolism are (SCFAs), predominantly and , which contribute to the acidic gut milieu without gas production, a trait consistent across bifidobacteria.

Health Implications

Probiotic Applications

Bifidobacterium longum is widely incorporated into commercial products, including yogurts, infant formulas, and dietary supplements such as the VSL#3 mixture, which contains multiple strains including B. longum for managing conditions like and . The U.S. has granted (GRAS) status to several B. longum strains, such as BORI and CBT BG7, for use in non-exempt term infant formulas at levels up to 10^8 colony-forming units (CFU) per gram of powdered formula and in conventional foods like dairy products at up to 10^9 CFU per serving. Established benefits of B. longum as a include alleviation of symptoms, such as reduced breath hydrogen response, , and , through by strains like NCC2705 when grown in lactose-containing media. It also improves frequency and bowel regularity; for instance, supplementation with B. longum BB536 has been shown to normalize frequency in elderly patients with . A 2025 synbiotic study involving with B. longum BB536 (2 × 10^9 CFU) and (4 g) daily for 4 weeks in healthy adults significantly increased frequency, volume, and Bristol Stool Form Scale scores while enhancing and . The safety profile of B. longum supports its use, with no adverse effects reported in studies at doses up to 2 × 10^11 CFU per day and no genes or significant resistance in evaluated strains. For efficacy, formulations require viable counts exceeding 10^6 CFU per gram to ensure sufficient delivery to the gut, as lower levels may not provide therapeutic benefits; typical supplements contain 1–10 × 10^9 CFU per dose. To enhance survival during gastrointestinal transit, B. longum is often delivered via encapsulation techniques, such as spray-drying with Eudraguard® biotic, , sodium alginate, and , achieving 97% encapsulation efficiency and protection against 0.1 M HCl and 0–3% salts while maintaining viability for weeks in storage. In pediatric applications, the strain YLGB-1496 (1.5 × 10^10 CFU per day) promotes intestinal balance by increasing beneficial species and while reducing pathogens like Bacteroides thetaiotaomicron, thereby supporting child microecology and alleviating gastrointestinal discomfort without adverse effects. For example, the strain 35624 is utilized in products targeting symptoms.

Pathogenic Potential

Bifidobacterium longum is primarily a commensal bacterium in the human gut microbiota, characterized by low virulence and a non-pathogenic profile in healthy individuals. As a probiotic, it rarely causes infections, with bacteremia associated with Bifidobacterium species, including B. longum, accounting for only 0.5–3% of anaerobic blood culture isolates in clinical settings. The incidence of such opportunistic infections among probiotic users remains extremely low, estimated at less than 0.1% based on large-scale neonatal prophylaxis programs where only isolated cases have been documented among thousands of treated infants. Reported cases of B. longum infections are infrequent and typically linked to administration in vulnerable populations. In preterm infants, bacteremia has been observed during efforts to prevent (NEC), with notable instances in the 2010s, including two confirmed cases of B. longum subsp. infantis bacteremia in 2014 traced directly to the administered via genomic analysis. Similarly, and cases have occurred in immunocompromised adults, such as a 2014 report of purulent due to B. longum in a with intestinal from , and multiple bacteremia episodes in elderly or cancer s during the 2013–2015 period. These infections often present as -like syndromes, though most patients recover with antibiotics and supportive care. Key risk factors for B. longum translocation and include underlying immunocompromise, such as in preterm neonates or adults with malignancies and autoimmune diseases, as well as gastrointestinal compromise like mucosal damage from or "leaky gut" conditions. High-dose supplementation in (ICU) settings further elevates the risk, as seen in neonatal cases where strains from commercial products were isolated from blood cultures, highlighting potential for bacterial dissemination via impaired barriers. In contrast, healthy individuals exhibit robust mucosal integrity that prevents such translocation. A 2025 safety evaluation using propidium monoazide (PMAxx)-qPCR showed that B. longum subsp. longum ZS-8 survives gastrointestinal at 1.53–6.90% but exhibits no long-term in healthy adults, with no viable cells detected in one week post-administration and stable composition. This method's ability to distinguish live from dead cells underscored the strain's safety in non-compromised hosts, supporting its overall low pathogenic potential outside high-risk scenarios.

Notable Strains

Bifidobacterium longum 35624

_Bifidobacterium longum subsp. infantis 35624 is a probiotic strain originally isolated from the ileal mucosa of a healthy human volunteer without gastrointestinal disease. This strain has been extensively studied for its role in gut health and was commercialized as the active ingredient in Align probiotic supplements in the United States starting in 2009 and as Alflorex in the European Union shortly thereafter. Its selection for commercial use stemmed from early research demonstrating its ability to survive gastrointestinal transit and colonize the intestinal epithelium effectively. Clinical evidence from randomized controlled trials supports the use of B. longum 35624 for alleviating (IBS) symptoms, particularly and . In a key multicenter trial involving women with IBS, supplementation with the strain at 1 × 10^8 CFU daily for four weeks significantly reduced composite scores for pain/discomfort, bloating/distention, and bowel dysfunction compared to . This symptomatic relief is linked to its properties, including upregulation of the regulatory interleukin-10 (IL-10), which helps normalize the cytokine profile in IBS patients and dampens excessive immune responses in the gut mucosa. At the mechanistic level, B. longum 35624 promotes gut health by adhering to intestinal epithelial s, such as the IEC-6 intestinal cell line, facilitating competitive exclusion of pathogens and enhancing mucosal colonization. Additionally, it modulates gut barrier integrity by increasing transepithelial electrical resistance and supporting protein expression in epithelial models, thereby reducing permeability and preventing translocation of inflammatory agents. These actions contribute to its overall efficacy in maintaining intestinal . Recent research has explored synergistic effects of B. longum 35624 in combination with other strains, such as B. longum 1714. A 2023 exploratory study in patients with moderate to severe IBS found that an eight-week regimen of the combination significantly improved anxiety and scores, alongside reductions in IBS severity, suggesting potential benefits for the gut-brain axis in this population.

Bifidobacterium longum BB536

_Bifidobacterium longum BB536 is a strain isolated from the of a healthy breast-fed in in 1969 by researchers at . Since its discovery, BB536 has been extensively studied for its stability in commercial products and health benefits, leading to its incorporation into fermented dairy items such as and milk-based drinks. Over five decades of research have established it as a multifunctional strain with applications in gut health and immune modulation. Clinical evidence supports BB536's role in improving digestive function, particularly in vulnerable populations. In elderly individuals with chronic , randomized controlled trials have shown that BB536 supplementation increases defecation frequency, softens stool consistency, and reduces associated upper abdominal symptoms, with effects observed after four weeks of daily intake. For , a double-blind crossover study demonstrated that BB536, combined with rhamnosus HN001 and , significantly alleviated gastrointestinal symptoms like and by enhancing through modulation. In allergic conditions, prenatal maternal intake of BB536 alongside M-16V, followed by postnatal infant supplementation, reduced the incidence and severity of and eczema in high-risk infants, as evidenced by lower SCORAD scores over 18 months. The mechanisms driving these benefits involve BB536's capacity to enhance Bifidobacterium diversity within the and generate metabolites that promote intestinal and environmental stability. Integrated and analyses reveal that BB536 colonization correlates with increased microbial diversity, reduced gut transit time variability, and elevated production of bioactive compounds that support epithelial integrity and . These metabolites encompass (SCFAs), detailed further in the section, which contribute to the strain's overall homeostatic effects on the host. Recent advancements highlight BB536's potential in synbiotic formulations. A 2025 single-arm involving healthy adults consuming synbiotic yogurt with BB536 and reported significant improvements in status and scores after eight weeks, attributed to microbiota-derived SCFAs and aromatic lactic acids that enhanced and .

Emerging Strains

Recent research has identified several novel strains of Bifidobacterium longum with promising therapeutic potential, particularly in modulating gut and addressing age-related conditions. These emerging strains, studied primarily between 2024 and 2025, demonstrate specific benefits in pediatric intestinal , metabolic regulation, and anti-aging effects, expanding the probiotic applications of the species. Bifidobacterium longum subsp. infantis YLGB-1496, isolated from human milk, has shown efficacy in improving intestinal microecology in young children through a randomized, blinded, placebo-controlled involving 100 participants aged 0–3 years. Administered at a dosage of 1.5 × 10¹⁰ CFU per day for three months, the strain significantly increased the relative abundance of beneficial bifidobacteria such as B. bifidum, B. kashiwanohense PV2, and B. longum while reducing Bacteroides thetaiotaomicron (p < 0.05). This modulation was associated with elevated fecal , including (30.54 vs. 26.32 μmol/g, p = 0.022) and total SCFAs (108.97 vs. 99.49 μmol/g, p = 0.02), suggesting enhanced microbial balance and potential indirect inhibition via competitive exclusion and immune support, as evidenced by reduced incidence (34.0% vs. 58.0%, p = 0.016). The intervention also lowered pro-inflammatory cytokines like IL-1β (51.98 vs. 59.15 pg/ml, p = 0.017) and elevated immunoglobulins, indicating a role in preventing common pediatric diseases without adverse effects. Bifidobacterium longum BL21, a subsp. longum isolate, has been investigated using multi-omics approaches for its capacity to alleviate gut disturbances and features of . In high-fat diet-induced obese mice, prior studies referenced in 2025 analyses demonstrated that BL21 supplementation rebalanced , regulated , and prevented progression. Complementary research in type 2 diabetic mouse models showed reduced fasting blood glucose levels and improved through modulation, with shifts favoring anti-inflammatory taxa. These findings, supported by 2025 human multi-omics data revealing enriched genera like Parasutterella, Parabacteroides, and Blautia alongside altered and pathways, underscore BL21's potential in metabolic regulation across models, though further strain-specific validation in contexts is ongoing. Heat-inactivated Bifidobacterium longum ZFML006 has emerged as a candidate for anti-aging interventions, particularly in a 2025 study using as a model. extended mean lifespan by 30.64% (approximately 9 days), reduced by 15.20%, and decreased accumulation by 49.92%, while improving thermotolerance (20.69%) and resistance (14.8%). These effects were linked to activation of MAPK and insulin/IGF-1 signaling pathways, with downregulation of daf-2 (1.75-fold) and akt-2 (1.40-fold), and upregulation of daf-16 (1.36-fold), sod-3 (2.51-fold), pmk-1 (1.32-fold), and skn-1 (1.40-fold). Antioxidant enhancements included elevated (2.47-fold), (1.30-fold), and (2.46-fold) activities, alongside a 10.6% reduction in , highlighting the strain's postbiotic potential via non-viable mechanisms. Safety evaluations of B. longum subsp. longum strains, including emerging isolates, utilized PMAxx-qPCR in a 2025 with 41 healthy adults receiving 1.0 × 10⁹ or 10¹⁰ CFU/day for 14 days. This method confirmed transient gastrointestinal survival (1.53–6.90%) and colonization without persistent dominance or translocation to systemic sites, as no viable cells were detected beyond one week post-administration and diversity remained stable. These results affirm the safety profile of subsp. longum strains for use.

Research Frontiers

Immune Modulation

Bifidobacterium longum exerts immunomodulatory effects by promoting the differentiation and expansion of regulatory T cells (Tregs) and enhancing production of the anti-inflammatory cytokine interleukin-10 (IL-10). studies have demonstrated that strains such as B. longum IM55 stimulate Treg induction through interactions with dendritic cells, leading to suppressed pro-inflammatory responses. Similarly, components derived from B. longum subsp. infantis, including methylated CpG oligodeoxynucleotides, have been shown to upregulate IL-10 secretion and expression in Tregs, contributing to . Randomized controlled trials (RCTs) involving multi-strain containing B. longum have reported a reduction in duration by approximately 1-2 days, alongside decreased symptom severity, attributed to these regulatory mechanisms. Along the gut-immune axis, B. longum enhances secretory (IgA) production to support mucosal barrier integrity and exclusion. In dextran sulfate sodium (DSS)-induced models, B. longum BL300 administration promoted IgA-coated , restoring and alleviating . Furthermore, B. longum strains reduce pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) in (IBD) models; for instance, B. longum BL-10 significantly lowered TNF-α levels while modulating Th1 cytokines like IFN-γ and IL-2. These effects underscore B. longum's role in dampening excessive immune activation at the intestinal interface. In strain-agnostic applications, multi-strain formulations including B. longum, such as VSL#3, have demonstrated in achieving remission in , a complication of IBD surgery, with RCTs showing sustained clinical improvement over . A 2024 study on a combination of B. longum 1714 and 35624 in (IBS) patients highlighted boosted pathways, including reduced peripheral and enhanced immunoregulation, correlating with symptom relief. In pediatric contexts, B. longum modulates risk by balancing Th1/Th2 immune responses during early infancy. Supplementation with B. longum subsp. infantis has been linked to regulation of the Th1/Th2 axis via the JAK-STAT pathway in murine models, potentially preventing atopic diseases by promoting Th1 dominance and reducing Th2-driven allergic sensitization.

Neuroprotective and Metabolic Effects

Bifidobacterium longum has shown promising neuroprotective effects through its influence on the gut-brain axis, particularly via the strain 1714. In a 2025 clinical study, supplementation with B. longum 1714 (1 × 10⁹ CFU/day for 8 weeks) increased tryptophan levels from 8.3 μM to 8.8 μM and elevated kynurenic acid concentrations, alongside an improved kynurenic acid: ratio, in healthy adults. These changes are linked to reduced anxiety and depressive symptoms, as kynurenic acid acts as a neuroprotective that mitigates in stress models. Additionally, B. longum 1714 has demonstrated in alleviating stress-induced , such as lowered IL-1β in murine models of anxiety, supporting its role as a . In metabolic health, the BL21 strain of B. longum subsp. longum aids in regulating obesity-related markers. A 2025 multi-omics involving and adults (2 × 10¹⁰ CFU/day for 8 weeks) revealed that BL21 supplementation altered β-diversity, enriching beneficial genera like Blautia and Butyricicoccus, while significantly reducing triglycerides by 0.21 mmol/L. This modulation restored microbiota imbalances associated with high-fat diets in prior models, decreasing and improving metabolism to counteract progression. Such effects position BL21 as a candidate for managing metabolic dysregulation. Anti-aging benefits are evident from the ZFML006 strain, where heat-inactivated cells extended Caenorhabditis elegans lifespan by 30.6% (mean increase of 9 days). This extension occurred through activation of the insulin/IGF-1 signaling pathway, including upregulation of the DAF-16 transcription factor (1.36-fold) and antioxidant genes like sod-3 (2.51-fold), alongside reduced reactive oxygen species by 10.6%. Concurrently, MAPK pathway activation enhanced stress tolerance, underscoring B. longum's potential in longevity. These effects stem from key mechanisms involving metabolism and short-chain (SCFA) production. B. longum metabolizes into indole derivatives like , which serve as precursors for serotonin synthesis in enterochromaffin cells, comprising 90% of bodily serotonin and influencing mood via the gut-brain axis. SCFAs, such as butyrate generated through microbial , modulate hypothalamic-pituitary-adrenal axis signaling, regulating and promoting while improving metabolic homeostasis by altering energy balance in the .

Genomics and Novel Applications

The of Bifidobacterium longum encompasses approximately 5,970 families across diverse strains, reflecting significant genomic diversity that supports adaptations to various host environments, while the core stabilizes at around 1,200 families essential for cellular functions. This structure highlights the species' plasticity, particularly in loci that vary among . In B. longum subsp. infantis, genomic adaptations for (HMO) utilization are prominent, featuring an expanded 43 kbp (Blon_2331-Blon_2361) with 30 genes, including glycosyl hydrolases such as sialidase, fucosidase, N-acetyl-β-hexosaminidase, and , alongside ABC transporters for HMO import. These elements, conserved across isolates, enable efficient HMO catabolism and contribute to the subspecies' dominance in the infant gut . Recent genomic characterization of B. longum subsp. nexus, proposed as a novel subspecies isolated from infant stool in 2025, reveals distinct phylogenetic clades and morphological traits, including predominantly rod-shaped cells in chains with visible septa, contrasting the typical Y-shaped branching of other subspecies. Analysis of its genome identifies unique genetic features associated with this rod morphology, potentially linked to cell division and septation genes that differentiate it from subsp. infantis and longum. Such insights underscore subspecies-specific evolutionary pressures in early-life colonization. Advancements in genomic tools have enabled targeted modifications in B. longum, such as CRISPR-Cas9 base editing systems that achieve high efficiency for altering metabolic pathways, including enhanced HMO utilization by knocking in or optimizing glycosyl hydrolase genes. These editable platforms facilitate strain engineering for improved probiotic traits, as demonstrated in studies optimizing carbohydrate catabolism loci. Metagenomic approaches further support tracking B. longum dynamics in fecal microbiota transplantation (FMT), where whole-genome sequencing and long-read metagenomics confirm long-term engraftment of donor-derived strains, persisting up to one year in recipients with recurrent Clostridioides difficile infection. This precise strain-level monitoring via tools like LongTrack reveals genomic stability and colonization patterns post-FMT. Novel applications leverage these genomic insights for therapeutic innovations. Extracellular vesicles (EVs) derived from B. longum NSP001, isolated in 2025 studies, ameliorate ulcerative colitis in mouse models by enhancing intestinal barrier integrity, reducing inflammation through T-cell modulation, and promoting short-chain fatty acid production in a microbiota-dependent manner. Synbiotic formulations combining B. longum subsp. infantis with HMOs, as explored in 2024 research, boost infant gut health by accelerating HMO consumption, elevating short-chain fatty acids, and suppressing pathogens, thereby supporting microbiome maturation. Additionally, combinatorial therapies pairing B. longum subsp. infantis with Lacticaseibacillus rhamnosus GG demonstrate anti-inflammatory effects in 2025 in vitro models, protecting epithelial barriers against inflammation-induced damage in immunocompetent systems mimicking gut pathologies. These vesicle- and synbiotic-based strategies highlight B. longum's potential in precision microbiome interventions.

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