Bifidobacterium Longum

• Gut microbiome balance
• Immune system modulation
• Intestinal barrier enhancement
• Neurological health support

• Reduction of inflammation
• Potential allergy symptom reduction
• Irritable Bowel Syndrome symptom improvement
• Constipation relief
• Potential mental health benefits
• Possible metabolic health support
• Infant gut health development
• Potential protection against certain infections

Bifidobacterium longum exerts its beneficial effects through multiple sophisticated mechanisms that contribute to gut health, immune modulation, and neurological function. One of its most distinctive features is its ability to metabolize a wide range of complex carbohydrates, particularly oligosaccharides that are indigestible by humans. This gives B. longum a competitive advantage in the gut ecosystem and allows it to produce beneficial metabolites.

B. longum is particularly adept at metabolizing human milk oligosaccharides (HMOs), especially the subspecies infantis, which has evolved specialized genetic pathways for HMO utilization. This ability makes it a crucial early colonizer of the infant gut and explains its predominance in breastfed infants. Through fermentation of carbohydrates, B.

longum produces short-chain fatty acids (SCFAs), primarily acetate and lactate, which are later converted to butyrate by other gut bacteria. These SCFAs serve multiple functions: they provide energy for colonic epithelial cells, create an acidic environment that inhibits pathogen growth, strengthen the intestinal barrier, and have anti-inflammatory properties. B. longum produces specific antimicrobial compounds that inhibit the growth of pathogenic bacteria.

These include organic acids, bacteriocins (antimicrobial peptides), and other antimicrobial substances that collectively help maintain a balanced gut microbiota by suppressing potential pathogens. A particularly important aspect of B. longum’s activity is its ability to strengthen the intestinal epithelial barrier. It enhances the expression and assembly of tight junction proteins between epithelial cells, reducing intestinal permeability and preventing the translocation of pathogens and toxins across the intestinal wall.

This ‘leaky gut’ prevention is crucial for reducing systemic inflammation and endotoxemia. B. longum has significant immunomodulatory effects, interacting with the gut-associated lymphoid tissue (GALT) to influence both innate and adaptive immunity. It promotes the development of regulatory T cells (Tregs) and increases the production of anti-inflammatory cytokines like IL-10, while reducing pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β when inflammation is excessive.

This helps maintain immune homeostasis and may contribute to its benefits in inflammatory and allergic conditions. B. longum modulates the gut-brain axis through multiple pathways, including the production of neurotransmitters and neuroactive compounds, the modulation of the vagus nerve signaling, and the reduction of systemic inflammation. It can produce gamma-aminobutyric acid (GABA), a neurotransmitter with calming effects, and may influence serotonin production through interaction with enterochromaffin cells.

This gut-brain modulation may explain its observed effects on stress, anxiety, and cognitive function in some studies. B. longum has notable antioxidant properties, producing enzymes such as superoxide dismutase that neutralize reactive oxygen species. This antioxidant activity may contribute to its anti-inflammatory effects and potential neuroprotective benefits.

In the context of allergic conditions, B. longum (particularly strains like BB536) has been shown to modulate Th1/Th2 immune balance, potentially reducing the excessive Th2 responses characteristic of allergic reactions. It also promotes the development of regulatory T cells that help maintain immune tolerance. B.

longum competes with pathogenic microorganisms for adhesion sites on intestinal epithelial cells, effectively preventing colonization by harmful bacteria through competitive exclusion. This mechanism is particularly important in preventing gastrointestinal infections and maintaining a balanced microbiota. For constipation relief, B. longum may help normalize gut motility through multiple mechanisms, including the production of SCFAs that stimulate peristalsis, modulation of gut hormone secretion, and potential effects on the enteric nervous system.

Strain-specific effects are particularly important for B. longum. Different strains have been shown to have distinct effects and mechanisms of action. For example, B.

longum 35624 has shown particular efficacy for IBS through specific immune modulation pathways, while B. longum BB536 has demonstrated strong anti-allergic properties. The subspecies distinction is also crucial, with B. longum subsp.

infantis having specialized mechanisms for HMO utilization and infant gut development, while B. longum subsp. longum has broader carbohydrate utilization capabilities and may have stronger effects on the adult gut-brain axis.

The optimal dosage of Bifidobacterium longum varies depending on the specific condition being addressed, the strain used, and individual factors. Generally, dosages range from 1 billion to 10 billion colony-forming units (CFU) per day for general health maintenance, while therapeutic dosages for specific conditions may range from 10 billion to 20 billion CFU daily. It’s important to note that efficacy is not solely determined by CFU count but also by strain specificity, viability at the site of action, and the particular health condition being addressed. Different strains of B.

longum (such as BB536, 35624) and subspecies (longum vs. infantis) have been studied at different dosages for various conditions.

Bifidobacterium longum is not ‘absorbed’ in the traditional sense of dietary supplements. Instead, its bioavailability refers to the percentage of live bacteria that survive the harsh conditions of the gastrointestinal tract to reach their site of action. B. longum has moderate acid and bile resistance compared to some other probiotic species, which affects its survival through the stomach and upper intestine.

Studies suggest that approximately 10-30% of orally administered B. longum may survive passage through the stomach and upper intestine, though this varies widely depending on formulation, strain characteristics, and individual factors such as gastric acidity and transit time. Once it reaches the intestines, B. longum can temporarily colonize the gut mucosa, with detectable levels persisting for 1-3 weeks after discontinuation in many individuals.

B. longum has demonstrated good adhesion to intestinal epithelial cells and mucus, which enhances its residence time and functional effects in the gut. This adhesion ability varies between strains and subspecies, with B. longum subsp.

infantis showing particularly strong adhesion to infant gut mucosa. The subspecies distinction is important for bioavailability considerations: B. longum subsp. infantis is particularly well-adapted to the infant gut environment and can efficiently utilize human milk oligosaccharides (HMOs), giving it a survival advantage in breastfed infants.

B. longum subsp. longum has broader carbohydrate utilization capabilities that help it survive in the more complex adult gut ecosystem. When administered to infants, B.

longum (particularly subsp. infantis) has shown good colonization of the developing gut microbiome, with some studies suggesting it may persist longer in infants than in adults due to the less competitive microbial environment and the availability of HMOs in breastfed infants.

Enteric coating: Protects probiotics from stomach acid, increasing survival rates by 30-60%, Microencapsulation: Shields bacteria from environmental stressors, potentially improving viability by 40-70%, Delayed-release capsules: Designed to release probiotics in the intestines rather than the stomach, Buffered formulations: Include compounds that neutralize stomach acid around the bacteria, Prebiotic inclusion (synbiotics): Provides nutrients that support probiotic growth and colonization, particularly fructooligosaccharides (FOS), galactooligosaccharides (GOS), and inulin, Human milk oligosaccharide (HMO) combinations: Particularly beneficial for B. longum subsp. infantis, as it has specialized genetic pathways for HMO utilization, Higher CFU counts: Compensates for die-off during transit, though quality and strain characteristics are more important than quantity alone, Refrigerated storage: Maintains viability before consumption, Consumption with meals: Food can buffer stomach acid and improve survival, Freeze-dried preparations: Maintain stability until hydration in the digestive tract, Selection of acid-resistant strains: Some strains of B. longum have naturally higher acid resistance than others

For maximum effectiveness, B. longum supplements are best taken with or just before meals, which helps buffer stomach acid and improve survival rates. When taken for general digestive health, consistent daily supplementation is more important than specific timing. Morning administration may be preferable for some individuals as gastric emptying tends to be faster in the morning, potentially allowing more bacteria to reach the intestines.

For mental health applications (anxiety, stress, mood), some preliminary research suggests that evening administration may align better with circadian rhythms of gut-brain communication, though this timing effect requires more research. For constipation relief, taking B. longum with adequate hydration and fiber intake may enhance its effects on bowel regularity. When used for allergic conditions, consistent daily use is more important than timing, though some practitioners recommend morning administration to align with natural circadian rhythms of immune function.

For infants, B. longum subsp. infantis is ideally administered shortly before feeding, particularly in breastfed infants, to allow the probiotic to reach the intestines alongside human milk oligosaccharides that serve as its preferred food source. When used as an adjunct to antibiotic treatment, B.

longum should be taken at least 2 hours apart from antibiotics to minimize direct killing of the probiotic bacteria. For maximum colonization potential, consistent daily use at approximately the same time each day is recommended, as B. longum typically remains in the gut for only 1-3 weeks after discontinuation. For inflammatory conditions, taking B.

longum with food may help reduce gastrointestinal inflammation through direct contact with the gut mucosa during digestion.

• Temporary digestive discomfort (gas, bloating)
• Mild abdominal cramping
• Increased bowel movements (usually temporary)
• Headache (rare)
• Increased thirst (rare)
• Constipation (rare, paradoxical reaction)
• Nausea (rare)
• Mild allergic reactions (extremely rare)

• Severely immunocompromised patients (e.g., those with AIDS, lymphoma, or undergoing long-term corticosteroid treatment)
• Patients with short bowel syndrome
• Individuals with central venous catheters
• Critically ill patients in intensive care units
• Premature infants (except for specific B. longum subsp. infantis strains that have been studied in this population)
• Patients with damaged heart valves or artificial heart valves
• Known hypersensitivity to Bifidobacterium species or any components of the probiotic formulation

• Antibiotics (may reduce probiotic effectiveness; separate administration by at least 2 hours)
• Immunosuppressants (theoretical increased risk of infection)
• Antifungal medications (may reduce probiotic effectiveness)
• Medications that decrease stomach acid (may increase probiotic survival but potentially affect colonization patterns)
• Anticoagulants/antiplatelet drugs (rare case reports of increased bleeding risk with certain probiotics, though not specifically with B. longum)

No established upper limit for B. longum. Doses up to 20 billion CFU daily have been used in clinical studies without significant adverse effects in healthy individuals. However, higher doses may increase the risk of side effects such as digestive discomfort without necessarily providing additional benefits.

The appropriate dose depends on the specific condition being treated, the strain being used, and individual factors. For general health maintenance, 1-10 billion CFU daily is typically sufficient. For infants, lower doses of 1-5 billion CFU daily of B. longum subsp.

infantis are typically used, with no benefit observed at higher doses in most studies. Individuals with compromised immune systems should consult healthcare providers before using any dose of probiotics. It’s important to note that safety concerns are more related to an individual’s health status than to specific dosage thresholds.

Bifidobacterium longum has an excellent safety profile and has been consumed in traditional fermented foods for centuries. It has Generally Recognized as Safe (GRAS) status in the United States and Qualified Presumption of Safety (QPS) status in the European Union. B. longum is one of the first bacterial species to colonize the human gut after birth and remains a key beneficial bacterium throughout life, reflecting its long evolutionary relationship with humans.

B. longum subsp. infantis in particular has been extensively studied in infants, including premature infants, with an excellent safety record when appropriate strains are used. There have been extremely rare cases of Bifidobacterium bacteremia (bacteria in the blood) in severely immunocompromised individuals or those with serious underlying health conditions, though B.

longum is less commonly implicated than many other probiotic species. While B. longum has a long history of safe use in foods and supplements, caution is advised in certain populations. Individuals with severe acute pancreatitis should avoid probiotics, as some studies have suggested potential harm in this specific condition.

Those with a history of endocarditis or artificial heart valves should consult healthcare providers before use. Diabetic patients should check probiotic supplement labels for added sugars. Individuals with milk allergies should ensure that dairy-free formulations are selected, as some B. longum products are cultured in dairy-based media.

Patients scheduled for surgery should inform their healthcare providers about probiotic use, as some practitioners recommend discontinuation 1-2 weeks before major surgical procedures. While B. longum has been consumed during pregnancy in traditional foods for centuries and is generally considered safe, pregnant women should still consult healthcare providers before starting any supplement regimen. Long-term safety studies on B.

longum have shown no adverse effects with continuous use over many years, making it suitable for ongoing supplementation in healthy individuals.

Brenner DM, Moeller MJ, Chey WD, Schoenfeld PS. The utility of probiotics in the treatment of irritable bowel syndrome: a systematic review. Am J Gastroenterol. 2009;104(4):1033-1049., Szajewska H, Canani RB, Guarino A, et al. Probiotics for the prevention of antibiotic-associated diarrhea in children. J Pediatr Gastroenterol Nutr. 2016;62(3):495-506., Ng QX, Peters C, Ho CYX, Lim DY, Yeo WS. A meta-analysis of the use of probiotics to alleviate depressive symptoms. J Affect Disord. 2018;228:13-19., Xiao JZ, Kondo S, Yanagisawa N, et al. Clinical efficacy of probiotic Bifidobacterium longum for the treatment of symptoms of Japanese cedar pollen allergy in subjects with seasonal allergic rhinitis. Allergol Int. 2007;56(1):67-75., Frei R, Akdis M, O’Mahony L. Prebiotics, probiotics, synbiotics, and the immune system: experimental data and clinical evidence. Curr Opin Gastroenterol. 2015;31(2):153-158.

Bifidobacterium longum for Prevention of Necrotizing Enterocolitis in Very Low Birth Weight Infants (ClinicalTrials.gov Identifier: NCT04183595), Effects of Bifidobacterium longum on Cognitive Function in Healthy Older Adults (ClinicalTrials.gov Identifier: NCT03624530), Bifidobacterium longum for Management of Depression and Anxiety (ClinicalTrials.gov Identifier: NCT03934827), Efficacy of Bifidobacterium longum in Children with Autism Spectrum Disorder (ClinicalTrials.gov Identifier: NCT04074590), Bifidobacterium longum for Prevention of Antibiotic-Associated Diarrhea in Children (ClinicalTrials.gov Identifier: NCT03895723)

Bifidobacterium longum has a substantial body of scientific evidence supporting several of its health benefits, with the strongest evidence for specific strains in particular applications. The research on B. longum spans multiple health domains, with particularly robust evidence in the areas of gut health, immune function, and emerging evidence for neurological benefits. For gut health, multiple clinical trials have demonstrated the efficacy of B.

longum (particularly strains like BB536) in preventing and treating various forms of diarrhea, including antibiotic-associated diarrhea and infectious diarrhea in both children and adults. The evidence for B. longum in Irritable Bowel Syndrome (IBS) is growing, with several randomized controlled trials showing benefits for symptom reduction, particularly when using specific strains like 35624 (formerly known as Bifidobacterium infantis 35624). Some studies have also shown benefits for constipation relief, though the evidence is more mixed in this area.

In the domain of immune function, B. longum has shown promise for allergic conditions, with the BB536 strain demonstrating efficacy for reducing symptoms of seasonal allergies and potentially preventing eczema in infants when administered to pregnant and breastfeeding mothers. Multiple studies have also shown immunomodulatory effects that may benefit inflammatory conditions. An emerging and particularly interesting area of research is the effect of B.

longum on the gut-brain axis and mental health. Several well-designed studies have demonstrated that specific strains of B. longum can reduce stress, anxiety, and depression symptoms while influencing brain activity patterns measured by electroencephalography (EEG). The strain 1714 has shown particular promise in this area.

For infant health, B. longum subsp. infantis has demonstrated significant benefits for developing a healthy gut microbiome, particularly in breastfed infants. The EVC001 strain has shown impressive results in reducing intestinal inflammation in infants and promoting the development of a healthy immune system.

The quality of evidence varies across different applications, with the strongest evidence coming from multiple well-designed randomized controlled trials for specific conditions like IBS, allergic symptoms, and certain forms of diarrhea. For newer applications like mental health benefits, the evidence is promising but still emerging, with several high-quality studies but a need for larger trials with longer follow-up periods. It’s important to note that the effects of B. longum are highly strain-specific, with different strains showing efficacy for different conditions.

The BB536, 35624, 1714, and EVC001 strains have the most extensive research support for their respective applications. Future research directions include larger, longer-term clinical trials, studies on specific mechanisms of action, exploration of strain-specific effects, and investigation of potential applications in neurological and metabolic disorders. Ongoing trials are exploring the potential benefits of B. longum for conditions such as necrotizing enterocolitis in premature infants, cognitive function in older adults, depression and anxiety, and autism spectrum disorder.