Probiotics

Definition- ‘‘Live microorganisms which when administered in adequate amounts confer a health benefit on the host’’ (WHO)

• Prebiotic - a substance (usually an oligosaccharide) that cannot be digested but does promote the growth of beneficial bacteria or probiotics
  • E.g. Oligofructose, Inulin, Galacto-oligosaccharides, Lactulose, Breast milk oligosaccharides
• Symbiotic - a substance containing both a prebiotic and probiotic.
• Ellie Metchnikoff, the first scientist who proposed the therapeutic use of lactic acid bacteria.

Why are Probiotics important for Human health?

  Key properties of probiotic

• Non-pathogenic, non-toxic and non-allergic.
• The organism must be fully identified: genus, species and strain
• Capable of surviving and metabolizing in upper G.I. tract e.g. Resistant to low pH, organic acids, bile juice, saliva and gastric acid
• Human in origin, genetically stable and capable of remaining viable for long periods in field condition.
• Able to modulate immune response and provide resistance to disease through improved immunity or by the production of antimicrobial substance in the guts.
• Good adhesion/ colonization to human intestinal tract and influence on gut mucosal permeability.
• Antagonistic against pathogenic organisms.
• Clinically proven health benefit, e.g. gastrointestinal disorders, diarrhoea, clostridium difficle colitis, antibiotics associated diarrhoea, acute gastroenteritis.
• Technologic properties for commercial viability such as stability of desired characteristics during processing, storage and transportation.

Examples of probiotics

Lactobacillus species -L. acidophilus, L. casei (rhamnosus), L. johnsonii, L. bulgaricus, L. plantarum, L. lactis

Bifidobacterium species- B. bifidum, B. longum, B. infantis, B. lactis, B. adolescentis.

Others- Bacillus cereus, Non-pathogenic Escherichia coli, Saccharomyces cerevisiae (yeast), Enterococcus faecalis

Streptococcus thermophilus.

FMT (Faecal Microbiota Transplant) cannot be considered probiotic, because this involves an undefined mixture of micro-organisms.

Mechanism of action

• Bioconversion , for example, sugars into fermentation products
• Production of growth substrates, like vitamins B and K, for other bacteria
• Direct antagonism to antimicrobial substances:
  • hydrogen peroxide
  • organic acids
  • Bacteriocin
  • Acidophilin
• Improve absorption of nutrients
• Production of β- D- galactosidase  enzymes that break down lactose .
• Reduction of inflammation, thus altering intestinal properties
• Stimulation of innate immune response

Foods containing Probiotics

• Milk, Soya milk, Milk products- Sour cream, Butter milk, Yoghurt, Fermented Indian foods like Idlis, Dosas, uttapam, Dhoklas, Vadas, Kadhi.

Genetically Engineered Probiotics

• A genetically modified Bacteroides ovatus and Xylan in small amounts  as a therapy to animals with colitis.
• ViBact (which is made up of genetically modified Bacillus mesentricus), which acts as an alternate to B-complex capsules.

Benefits of Genetic engineering:

• Strengthen the effects of existing strains
• As vector for vaccines and growth hormones

Clinical application of probiotics

results are promising but not yet conclusive.

• Diarrheal Illness - treatment and prevention
• Prevention of antibiotic-associated diarrhea (AAD)
• Genito-urinary.
• Inflammatory bowel disease (ulcerative colitis,CD)
• Lactose intolerance
• Cancers
• Food allergies
• Eczema
• Necrotizing enterocolitis

Allergy

• Atopic eczema, Dermatitis, Allergic rhinitis, Asthma, food allergies with peanuts, tree nuts, soy, wheat gluten, fish
• Atopic children tend to have a degree of dysbiosis with more clostridia and fewer bifidobacteria 
• é IgE thought to be caused by a skewed balance between T helper type 1 and T helper type 2 cells
• Probiotics improving the Th1/Th2 balance in favor of a predominance of Th1 cells

Genitourinary

• Recurrent Candida Vaginitis and Bacterial Vaginosis have been successfully treated by administration of both oral and vaginal Lactobacilli
• Vaginal pessaries with 1 billion colony forming units

IBD

• IBD is associated with a breakdown of the normal barrier function provided by the gut epithelial lining and its associated with decreased mucus commensal bacteria.
• Use of probiotics and prebiotics giving good results in maintaining remission in UC but not of much in CD
• Nissle strain - Only probiotic recommended in ECCO guidelines as effective alternative to mesalazine in maintenance of remission in UC patients.
• Good evidence for preventing an initial attack of pouchitis, and relapse of pouchitis after the induction of remission with antibiotics
• Can be recommended in mild pouchitis, or as maintenance therapy for those in remission
• Usually 1x10⁹, or 1 billion colony forming units (CFU) is a good daily dose

IBS

• Prebiotics relieve constipating symptoms-
  • Increased bacterial mass and osmotic water-binding capacity  making stools bulky
  • Increased stool frequency and make stools softer
• A reduction in abdominal bloating and flatulence as a result of probiotic treatments is a consistent finding
• Some strains may ameliorate pain and provide global relief (B. infantis 35624)
• Dose - 10⁸ cfu of the freeze-dried probiotic bacteria B. infantis spec.

Immunoregulation

• Probiotics helps to Increase IgA production by B- cells        
• Has antiviral property, induce NO synthase (a virus infected cell death mechanism)
• Production of gamma intereferon, TNF-alph,IL-1 by mononuclear cells incubated with Lactobacillus. Increase cytotoxic potential of NK cells, increasing IL-10 synthesis thus preventing acute infectious disease
• Adherant Lactobacilli and Bifidobacteria significantly increase phagacytosis.

Anticancer effects

• Probiotics have been shown to improve biomarkers associated with colorectal cancer
• 5-wk supplementation of probiotics reduced the urinary excretion of aflatoxin, a marker for hepatocyte carcinogenesis, and symbiotic consumption for 12 wk significantly reduced colorectal cancer risk

Necrotizing Enterocolitis

• Reduces the risk of necrotizing enterocolitis in preterm neonates.
• Meta-analyses have also shown a reduced risk of death in probiotic-treated groups, although not all probiotic preparations tested are effective.
• NNT to prevent one death from all causes by treatment with probiotics is 20.

Adverse effects

• Probiotics side effects, if they occur, tend to be mild and digestive symptoms. (such as gas or bloating).
• May cause infections, especially in immuno- compromised patients.
• Diabetic patients should be cautious about taking probiotic drinks available in the market as they contain high level of sugar.

Probiotic products taken as a dietary supplement are manufactured and regulated as functional foods, not drugs.

• Probiotics supplements are not necessary for normal, healthy individuals.
•  In healthy individuals, daily consumption of probiotics rich foods, particularly fermented dairy products like yoghurt adequately supplies the amount of probiotics required to maintain a healthy digestive system and overall wellbeing.
• A diet high in starches and fibre provide prebiotics, which keep a healthy population of probiotics in our intestines.

Challenges

• Retention of viability of the probiotic bacteria - The numbers of viable bacteria continually decrease with time during refrigerated storage
• A serious problem of shelf instability had been encountered with dried Cultures.
• Manufacturer needs to incorporate an excess of cells at the time the tablets are manufactured. This practice increases the cost and makes the use instructions inaccurate
• Extreme temperatures, high pressure, shear forces can destroy the preperations
• Survival of most bifidobacteria in most dairy products is poor due to low pH and/or exposure to oxygen
• Difficulty in assessment of efficacy of probiotics
• Currently in India, probiotics are characterized as functional food
• Regulated by food laws - FSSA (eatables regulations covering nutraceuticals, foods and dietary supplements)
• ICMR and DBT have formulated guidelines for probiotics being marketed as foods.
• These guidelines specify the criteria when launching a probiotic food, labelling requirements
• They describe parameters to define a product as 'probiotic'.
• May be used as a reference to establish probiotic standards in the country by the FSSAI
• Probiotics delivered in food MAY NOT be tested in PHASE 3 studies, unless the product makes a specific health claim wherein it becomes necesssary to carry out Phase 3 studies.