5. Prebiotics, probiotics & the human intestinal microbiota Flashcards

1
Q

Microbiota vs Microbiome

A

Microbiota – microbial organisms that live on or in the human body

Microbiome – collective genomes of all the microbes in the microbiota

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2
Q

Human intestinal microbiota [1]

A
  • Humans colonised by many micro-organisms, residing on or in various organs, including the skin & GIT
  • Hundreds of species of bacteria are present in the human gut, many of which are beneficial for the host – balance of these micro-organisms are require for normal GI function
  • Regulator of host metabolic & immune functions
  • Protects against invasive pathogens e.g. Clostridium difficile (colonisation resistance)
  • Associations between specific characterisation of intestinal (& other body site) microbiota & certain human disease conditions are being explored
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3
Q

Human intestinal microbiota [2]

A

Can be altered by e.g.

  • Dietary shifts
  • Medicines (immunosuppressants, antibiotics)
  • Results in dysbiosis (alterations in the microbiota)
  • For some individuals, recovery from disturbance may take > 6 months
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4
Q

Human intestinal microbiota [3]

A

Implications not full understood:

  • Is disease (e.g. IBD) due to microbial community disturbance?
  • How can the microbial community disruption on colonisation resistance e.g. against Salmonella?
  • Dysbiosis can lead to overgrowth of many pathogenic bacteria esp. C. difficile
  • CDAD (C. difficile-associated diarrhoea) in particular is associated with serious adverse events, including electrolyte disturbances, volume depletion, pseudomembranous colitis, toxic megacolon & in rare cases, death
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5
Q

Prebiotics [1]

A
  • Non-digestible food ingredients that beneficially affect the host through stimulating growth &/or activity of certain ‘beneficial’ bacteria in the colon of the GI tract
  • E.g. Fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS), inulins (NB: not insulin), lactulose (galactose + fructose)
  • Inulins are polysaccharides comprising mostly fructose units (20 to 1000s) & usually with a terminal glucose unit
    + Short chain inulins sometimes called FOS
  • Inulins are naturally occurring carbohydrates produced & stored by many plants & used by them as an energy source
  • Inulins/FOS (aka oligosaccharide fructans) occur naturally in some plants, particularly some fruits (e.g. bananas) & vegetables (e.g. onions, garlic, asparagus, leeks, chicory, Jerusalem artichoke
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6
Q

Prebiotics [2]

A
  • Inulin(s)/FOS are not digested by enzymes in the upper GIT – FOS can resist hydrolysis by salivary & intestinal digestive enzymes because of the configuration of their glycosidic bonds
  • They reach the colon intact, where they are metabolised by bacteria, producing lactic acid – reduces pH which favours growth of ‘beneficial’ bacteria
  • In clinical studies, ingestion of fructo-oligosaccharides increased the relative proportion of Bifidobacteria species & reduced the concentration of ‘harmful’ bacteria (e.g. Clostridia spp) in faeces
  • So, there is evidence that prebiotics can modify the composition of the microflora in the colon, &/or effect some metabolic activities of the microflora
  • But, currently little evidence that leads to beneficial health outcomes
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7
Q

Probiotics [1]

A
  • Live preparations of some types of ‘beneficial’, non-pathogenic micro-organisms (mainly bacteria or yeast), intended to normalise imbalances in host’s microflora & replace ‘harmful’ bacteria in the gut
  • “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”

Key elements:

  • Microbial
  • Viable
  • Beneficial to health (or intended to be so)
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8
Q

Probiotics [2]

A

Bacteria – numerous species used:

  • Lactobacillus species e.g. L. acidophilus, L. casei, L. fermentum, L. gasseri, L. johnsonii, L. paracasei, L. plantarum, L. rhamnosus, L. salivarius; part of lactic acid bacteria group; Gp+ve, acid-resistant
  • Some Bifidobacteria spp., e.g. B. adolescentis, B. animalis, B. bifidum, B. breve, B. longum
  • Streptococcus salivarius subsp. thermophilus, Enterococcus faecium

Yeast – microscopic fungi:
- Saccharomyces boulardii, Saccharomyces cerevisiae

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9
Q

Probiotics [4]

A

-Typically, probiotic products comprise combinations of ~5 – 15+ different micro-organisms (species/strains of the same species)
- E.g. Proprietary probiotic blend providing 50 billion CFU (CFU = colon-forming units), each ampoule contains:
+ Lactobacillus acidophilus (strain ATCC-SD5221) 10 billion CFU
+ Lactobacillus paracasei (strain Lpc-37) 10 billion CFU;
+ Bifidobacterium lactis (strain Bl-07) 10 billion CFU;
o Bifidobacterium lactis (strain Bl-04) 9 billion CFU;
+ Bifidobacterium bifidum (strain Bb-02) 1 billion CFU etc
- Strain – genetic variant/subtype of species
+ Different strains can have different properties/characteristics e.g. adhesion, resistance
- Sometimes in combination with other ingredients e.g. vitamins, minerals, herbal ingredients e.g. cranberry fruit extract

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10
Q

Probiotics [4]: Quality

A

Wide variation in context/number of viable cells – expressed as CFU across different products

Depending on species, strain, indication, user, 1bn – 40bm CFU/d

  • Usually 5+bm CFU/day – evidence is strain specific
  • Actual contents differ from label e.g. contain fewer cells
  • Misspelling of names of bacterial species/strains or incorrect names
  • Similar issues with veterinary probiotics

USP standards:

  • USP has developed & published monographs of probiotic strains in the Food Chemical Codex (FCC) – submissions for other microbial strains are in progress
  • Monographs include description/definition, standards for identification, assay method & acceptance criteria, limits for contaminants, labelling, packaging & storage

To refrigerate or not refrigerate:

  • Many bacterial species contained in probiotic products are sensitive to heat & moisture
  • Some organisms killed by heat, moisture, encourages growth, but organisms subsequently die due to lack of nutrients & environment
  • Freeze-dried, blister packed probiotics generally do not need to be refrigerated or kept in low humidity environments, but should not be exposed above room temperature
  • Care with ordering products online/mail order
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11
Q

Probiotics [5]

A
  • Live organisms present in some fermented milk products e.g. yoghurt, but may not be well-defined in terms of strain composition & stability, require refrigeration
  • Expert panels recommend that such foods are best described as “containing live & active cultures”, but should not be called probiotic
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12
Q

Probiotics [6]: Claims (7)

A
  1. “Super probiotic designed to restore & correct stomach bacteria”
  2. “Aids in maintaining a normal healthy immune system”
  3. “Helps maintain normal healthy urogenital flora”
  4. “Helps reduce the symptoms of medically diagnosed IBS”
  5. “Helps maintain normal bowel function”
  6. “Support to relieve diarrhoea”
  7. “Support for preventing gastric problems”
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13
Q

Probiotics [7]: Claims/marketed uses (7)

A
  1. Supporting a healthy gut microbiota (not yet scientifically defined in terms of microbial composition)
  2. Restoring a healthy gut microbiota after antibiotic treatment
  3. Enhancing the immune system
  4. Prevention & treatment of diarrhoea, including ‘traveller’s diarrhoea’, antibiotic-treatment-associated diarrhoea, acute diarrhoea
  5. Prevention & treatment of vaginal & UTIs
  6. Prevention & treatment of allergic conditions
  7. Treatment of inflammatory bowel conditions, e.g. IBS, ulcerative colitis, Crohn’s disease
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14
Q

Probiotics [8]: How might they work? (6)

A

Possible modes of action for probiotics include:

  1. Aid maintenance of community of beneficial microorganisms
  2. Help restore beneficial bacteria after disruption (e.g. with antibiotic treatment)
  3. Stabilise GIT’s barriers against ‘bad bacteria’, or produce substances that inhibit growth of ‘bad bacteria’
  4. Outcompete undesirable microorganisms, e.g. for nutrients
  5. Stimulate the immune response

NB:

  • Probiotics may act in several ways
  • Different probiotics may act in different ways
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15
Q

Probiotics [9]: Evidence - caveats

A

Consider the following when reviewing clinical evidence for probiotics:

  • Few studies undertook pharmaceutical analysis of the product/material to confirm identity, viability, quantify contents, checks for presence/absence of contaminants
  • Many studies have methodological limitations, which means that the results have to be interpreted cautiously - Evidence is strain-specific – results of one study should not be extrapolated to products containing other strains/species
  • More research needed on effects of specific strains, species, dose regimen etc
  • Also, any new trials since Cochrane review, other systematic reviews
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16
Q

Probiotics [10]: Safety

A
  • Generally regarded as safe – non-pathogenic bacteria/yeast
    + Reported ADRs typically minor, usually GI symptoms
  • Isolated reports of infections e.g. bacteraemia, endocarditis, septicaemia, pneumonia, deep abdominal (abscesses) associated with probiotics in neonates, severely debilitated/immunocompromised children, esp those with underlying risk factors, including central venous catheter use – PBs contraindicated
  • Also, rare reports, of opportunistic infections in elderly patients following regular use of probiotics – potential for allergic reactions
  • Systematic review of RCTs (n=347) of short term use of antibiotics (particularly Lactobacillus species) found no statistically significant differences in the overall number of ADRs, including serious ADRs
  • Long term use, super high doses, drug interactions, transference of antibiotic resistance genes
17
Q

Symbiotics

A
  • Products containing both pre- & probiotics
  • Ingredients of some products are complementary
  • In some products, prebiotic ingredients are selected specifically to support the growth of the probiotic bacteria
  • View that the term ‘symbiotic’ should be reserved to products that are synergistic
18
Q

Faecal Microbiota Transplantation (FMT)

A
  • Transfer of faecal material from a healthy individual to a diseased recipient
  • Restoration of colonic microbial diversity
  • Donated ‘healthy’ stool samples transplanted into patients via nasogastric tube, colonoscopy, retention enema, or orally using capsules containing freeze-dried material

Formal standard practice-guidelines published

  • Donor selection & screening
  • Preparation of materials
  • Administration
19
Q

FMT: Efficacy

A

Fresh stool, refrigerated:

  • 100g stool diluted with 300 mL water
  • Emulsified
  • Strained through gauze
  • Resulting suspension given fresh air or frozen & thawed
  • Drawn into syringes & given as enema

Effective in recurrent Clostridium difficile

  • Clinical resolution rate 70 – 90% with 1 or 2 FMT procedures
  • No clear consensus on place in therapy
  • EU & Can: 2nd recurrence
  • Frozen material (shit) as good as fresh material (shit)
  • Efficacy may vary depending on the route of administration
  • Under investigation in other conditions where gut microbiome hypothesised to play a role e.g. IBD, IBS, MS, Parkinson’s, obesity, metabolic syndrome & others
20
Q

FMT: Safety

A
  • ADRs include constipation, bloating, flatulence, diarrhoea, cramping – usually short lived (48h)
  • Serious ADRs are rare, including in elderly or immunocompromised patients
    + Caution with FMT in IBD patients with CDI – may get IBD flare
  • Long-term safety unknown – needs further study
21
Q

FMT: Future

A
  • Rapid evolution of FMT products – moving from natural blended stool suspension to standardised, quantifiable, microbiota suspensions that can be produced under GMP & highly lyophilised encapsulated full spectrum microbiome (FSM) products
  • Synthetic FMT products also in development e.g. cultured stool substitutes
  • Paradigm FMT in therapeutics – bacteria not only potential pathogens, a diverse bacterial community is essential for host health
  • US NIH Microbiome Project aims to characterise the compositional range of ‘normal’ microbiome of different body sites of healthy individuals, and of microbiome in 3 health conditions
    + IBD
    + T2DM
    + Pregnancy – vaginal microbiome