Probiotic Series: Bifidobacteria Infantis

Overview

• Family: Bifidobacteriaceae
• Genus: Bifidobacterium
• Species: longum, subspecies: infantis
• Recently reclassified together with Bifidobacterium longum as Bifidobacterium animalis lactis^[1,2]

Strains: B.infantis 35624^[3-6] (Align, Proctor and Gamble, Cincinnati, OH), Unknown strain of B. infantis included in VSL#3^® probiotic blend^[6,7] (Sigma-Tau Pharmaceuticals, Inc., Towson, MD), Strain EVC001^[8] (Evivo, Evolve BioSystems), B. infantis CCRC 14633 & B. infantis CCRC 14661^[9], B. infantis CGMCC313-2^[10] (Kexing Biotech Company Limited, Shenzhen, China)

Normal Location(s)

• Human infant gastrointestinal tract. The presence of Bifidobacteriaceae members in the infant gut can reach 90% of the total gut microbiota.

Normal Function(s)

• Increases riboflavin (B2) production soymilk and milk products during fermentation productions.^[11]
• Thiamine (B1), nicotinic acid, folic acid
• B12, B6
• Biotin ^[12]
• The major metabolizer of human milk in infants – particularly human milk oligosaccharides (HMOs) – only B. infantis can digest all HMO structures

Enzymes it produces

• Alpha-L-Fucosidases – breaks down fucoses in HMOs
• Alpha-Sialidases
• Many other glycoside hydrolases
• Beta-galactosidases,
• Beta-hexoaminadases
• HMO transporters (on membrane)
• endo-β-N-acetylglucosaminidase – N-deglycosylation of human milk
• enzymes that deconstruct milk glycans (break down products of gangliosides)^[13]

Special functions/things that distinguish it from other species or strains

• It is the primary colonizer of the infant gut and grows better than any other bacteria in infant gut. It has the unique ability to digest and consume human milk oligosaccharide structure. Most important in metabolizing mother’s milk in infants!
• Anti-inflammatory in premature intestinal cells
  • “B. infantis supernatant suppressed the exuberant production of the proinflammatory cytokines IL-6 and IL-8 and toll-like receptors TLR2 and TLR4 triggered by lipopolysaccharide and IL1β in the immature tissue explants”^[13]
  • Decreases TNF-a and IL6 (proinflammatory) and increased IL-10 (anti-inflammatory) in psoriasis and chronic fatigue syndrome patients.^[5]
• Decreases intestinal permeability to bacteria^[13]
• In premature infants: A combination of human milk and infantis increases B. infantis and decreases Enterobacteriaceae in the feces ^[13]

Summary of Association with Disease(s)

Listed below are possible uses for different strains of B. infantis with some applications backed by human trials and commercialized for human use. Other uses are theoretical in humans and only investigated in animal models. For more information, see “Evidence for Use” sections that follow.

Symptom reduction in:

• Atopic dermatitis
• Psoriasis
• Ulcerative colitis
• Irritable Bowel Syndrome

Preventative for:

• Pouchitis after surgical ileal anal pouch formation
• Necrotizing enterocolitis

Additional potential uses for:

• Improving vaccine responses in term infants
• Immune modulation as an anti-inflammatory agent
• Mood regulation and reduction of depressive symptoms in mouse model
• Inhibiting allergen-induced airway asthma and food allergies in mouse model

Factors That Influence Its Normal Role (Eg. Antibiotic Use, Diet, Environmental Factors, Etc.)

1. infantis proliferates in human milk, particularly in HMOs. Human milk gangliosides have a selective “prebiotic” effect.^[13]

Where Its Found: Supplements and Natural/Dietary Sources

 “Food” stuffs

• Infant formula: Natren Life Start Infantis, 2.5-Ounce utilizes the NLS strain
• Yogurt, sauerkraut, olives, salami, cheese

Supplements:

• infantis 35624, Align (Proctor and Gamble, Cincinnati, OH)
• Evivo
• Unknown strain of B. infantis included in VSL#3^® probiotic blend (Sigma-Tau Pharmaceuticals, Inc., Towson, MD)
• Probiotic Formula, Phillips Colon Health, Florajen3, Primadophilis Bifidus

Special considerations of supplementation (how to administer/dose)

• Align^[3]:
  • PO, 1 capsule (4 mg), daily
  • Suggested uses: restoration of intestinal flora, post-antibiotic diarrhea, and prevention of post-antibiotic candidiasis
  • C/I: Immunocompromised patients and GI wall perforation
  • Mechanism of Action: “Restores normal bowel flora that inhibits growth of harmful bacteria; stimulates local immunity’ promotes water resorption in colon”
• Evivo^[8]:
  • A supplement powder meant to be mixed into breast milk
  • Sachets contain Lactose and activated B. infantis EVC001
  • 8 billion CFU per sachet
  • Direction mix 1 sachet with 3-5 mL of breast milk, feed to baby with syringe Once daily.
  • Store in freezer
  • “First and only clinically proven probiotic for babies” – only clinically proven to restore B. infantis and reduce “bad” bacteria linked to a higher risk of health issues for infants, now and later in life.

Multi-ingredient

• VSL#3^[7] with 8 different strains of live bacteria (Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus delbrueckii subsp. Bulgaricus, Streptococcus thermophiles)
  • Advised to be used under medical supervision but does not need prescription.
  • Kept refrigerated or can be left at room temp up to 77 F up to 2 weeks
  • Do not take with hot foods or liquids
  • Takes up to 30 days to start feeling full benefits
  • Approved uses: IBS, UC, Pouchitis
  • Capsules for IBS:
    • 5 billion CFU/ capsule
    • 2-4 capsules a day depending on symptoms with or without food.
  • Powders for UC
    • 1-4 packets depending on prescription
    • 2 types of packets
      • VSL#3 Unflavored (450 billion CFU/packet)
      • VSL#3-DS (900 billion CFU/sachet)
    • Other supplements that contain both bifidobacterium infantis & lactobacillus acidophilus: Probiotic Formula, Phillips Colon Health, Florajen3, Primadophilis Bifidus

Evidence for Use in Dermatology

Atopic Dermatitis

Farid et al 2011 showed that administration of 7 strains of probiotic bacteria – 1 x 10⁹ CFU twice daily over 8 weeks - and fructooligosaccharide in 40 infants showed improvement of atopic dermatitis^[14,15].

Psoriasis

Groeger et al. 2013 showed that 1 x 10¹⁰ CFU of B. infantis 35624 for 8 weeks for oral administration in adults 18-60 year olds significantly lowered proinflammatory CRP and increased anti-inflammatory cytokine IL-10^[5].

Evidence for Use Beyond Dermatology

Irritable Bowel Syndrome (IBS)

Significant reductions in IBS symptoms in adults of abdominal bloating, cramping, and bowel movement difficulty compared to placebo and other lactobacillus species. ^[4,6]

Ulcerative Colitis (UC) and Pouchitis

VSL#3 probiotic blend which contains B. infantis has been studied for use in ulcerative colitis and prevention of pouchitis in UC patients that have surgical ileal anal pouch. VSL #3 claims that its probiotics work by increasing the amount of “good” commensal bacteria thereby preventing microbial dysbiosis characteristic of UC, and combating intestinal permeability and pathogenic colonization of gut barrier, and decreasing inflammation. Because VSL #3 blend is a combination of bacterial strains it is unclear what absolute effect B. infantis specifically has on UC disease progression. In one study in rat models with TNBS-induced colitis, oral feeding of B. infantis indicated significant reduction in inflammation, mucosal damage, and preservation of goblet cells as compared to control animals.^[16]

Other enteric pathology

Other benefits to the immature gut are numerous. In one study, B infantis administration increased growth in very low birth weight infants exposed to antibiotics.^[17] In addition, B infantis has been shown to be anti-inflammatory in many in vitro and animal studies reviewed by Underwood et al. 2015. In summary, B. infantis was modeled to decrease the risk of necrotizing entercolitis (NEC) in premature infants through several mechanisms; by suppressing pro-inflammatory cytokines that are involved in pathophysiology of NEC pathology, suppressing NEC-causing bacteria like Cronobacter sakazakii in mouse models, and decreasing intestinal permeability to microbes.^[13]

Immune system development and function

1. infantis has been associated with regulating an immune balance by promoting a healthy immune response against pathogens but attenuating pathological inflammatory responses that mediate processes like inflammatory bowel disease or allergies. Having B. infantis colonization of the infant gut produces an early introduction of antigens that allow for maturing of innate immune response. In a study with term infants in Bangladesh, it was found that gut colonization with B. infantis was associated with increased vaccine responses (oral polio, tuberculosis, and tetanus), had better weight gain, and increased thymic index.^[13]

The strain CGMCC313-2 was shown in one study to have a protective effect on mouse models of asthma and food allergy, attenuating allergic inflammation and inhibiting secretion of allergen-induced IgE, IL-4, and IL-13. Mouse models were created through allergen sensitization to produce ovalbumin-induced airway asthma and beta-lactoglobin-induced food allergy states.

Mood and Behavior

Studies of Desbonnet et al. 2008 and 2010 showed that B. infantis treatment may have the potential to shift moods. The 2008 study in rats resulted in attenuation of inflammatory immune responses, and elevation of serotonergic precursor, tryptophan.^[18] The latter study showed that B. infantis treatment used on rat maternal separation model of depression in setting of acute stressor of forced swim test resulted in normalization of immune response, reversal of behavior deficits, and restoration of noradrenaline in brainstem.^[19]

Chronic Fatigue syndrome, which is an inflammatory disease, was found to modifiable by B. infantis 35624. The strain reduced plasma levels of inflammatory markers C-reactive protein levels, IL-6, and TNF-alpha.^[5]