Probiotics and Prebiotics

Probiotics and Prebiotics

1. Definition & overview

• The human microbiome is the genetic repertoire of the ecosystem of microbes (bacteria, viruses including phages, and sometimes archaea, fungi, and microbial eukaryotes) that coexist at a given body site; the microbiota is the collection of those microbes at a specific site (oral cavity, oesophagus, skin, gut, vagina) (G&G 14e Ch.6, p.119).
• Microbial genes outnumber human germline genes by ~10⁴-fold (>200 million microbial genes vs ~20,000 human genes); microbial cells (mainly gut bacteria) exist in an approximately 1:1 ratio with human cells (G&G 14e Ch.6, p.119).
• More than 90% of the gut microbiota belong to two phyla, Bacteroidetes and Firmicutes; person-to-person variability in the gut microbiome exceeds 90%, forming a continuum rather than discrete "enterotypes" (G&G 14e Ch.6, p.119).
• Establishment begins at delivery (vaginal vs caesarean shapes early colonization); after weaning an individual microbial "signature" is established that persists long term, though diet, geography, lifestyle, circadian rhythm, age, season, and xenobiotics modulate composition (G&G 14e Ch.6, p.119).
• The rationale for probiotic/prebiotic therapy: diarrhoeal illness and antibiotic use disturb the population, composition and balance of gut microflora; recolonization of the gut by non-pathogenic, mostly lactic-acid-forming bacteria and yeast is believed to help restore that balance (KDT 8e Ch.49, p.732).
• Probiotic — "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host" — the FAO/WHO (2001/2002) working-group definition, reaffirmed by the ISAPP 2014 consensus panel (Hill et al.) (FAO/WHO 2001; Hill et al., Nat Rev Gastroenterol Hepatol 2014;11:506 [PMID 24912386]).
  • KDT's working description: probiotics are "microbial cell preparations, either live cultures or lyophilised powders, intended to restore and maintain healthy gut flora or have other health benefits" (KDT 8e Ch.49, p.732).
  • Three operational criteria are implicit in the definition: the organism must be alive (viable) at the point of administration, given in a defined, adequate dose (CFU), and shown to deliver a measurable health benefit in a controlled study (Hill et al. 2014 [PMID 24912386]).
• Prebiotic — "a substrate that is selectively utilized by host microorganisms conferring a health benefit" (ISAPP 2017 consensus; Gibson et al., Nat Rev Gastroenterol Hepatol 2017;14:491 [PMID 28611480]).
  • The 2017 update broadened the concept beyond the original "non-digestible, selectively fermented carbohydrate" wording, but the prototypical prebiotics remain the fermentable carbohydrates inulin, fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS) and lactulose (ISAPP 2017 [PMID 28611480]).
  • In KDT, dietary fibre and the soluble fibres (ispaghula/psyllium, gums, pectins) function as endogenous prebiotic substrates — they are "largely fermented in colon," increase bacterial mass, and "support bacterial growth in colon which contributes to the faecal mass" (KDT 8e Ch.49, pp.722–3).
  • Lactulose (a semisynthetic disaccharide of fructose + galactose) is a paradigm prebiotic laxative: not digested/absorbed in the small intestine, it is broken down by colonic bacteria to osmotically active, weakly acidic short-chain products; the acidification underlies its use in hepatic encephalopathy (lowers stool pH, traps NH₃ as non-absorbed NH₄⁺) (KDT 8e Ch.49, p.725).
• Synbiotic — "a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host" (ISAPP 2019 consensus; Swanson et al., Nat Rev Gastroenterol Hepatol 2020;17:687 [PMID 32826966]).
  • Two subsets: a complementary synbiotic = an independently-evidenced probiotic simply co-formulated with an independently-evidenced prebiotic; a synergistic synbiotic = a substrate specifically designed to be selectively utilized by the co-administered microorganism (Swanson et al. 2020 [PMID 32826966]).
• Postbiotic — "a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host" (ISAPP 2021 consensus; Salminen et al., Nat Rev Gastroenterol Hepatol 2021;18:649 [PMID 34002101]).
  • The definition deliberately excludes purified microbial metabolites (e.g., isolated butyrate or lactic acid), vaccines, substantially purified components (proteins, peptides, exopolysaccharides), cell-free filtrates lacking biomass, bacteriophages/viruses, and chemically synthesized compounds — a postbiotic must contain inactivated microbial cells or cell fragments (Salminen et al. 2021 [PMID 34002101]).
• Faecal microbiota transplantation (FMT) — transfer of a processed stool suspension from a screened healthy donor into a recipient to reshape a dysbiotic microbiome toward a healthy-donor-like state; the broadest "whole-community" microbiome intervention (G&G 14e Ch.6, pp.120, 125–6).
• Spectrum of microbiome-directed therapeutics, narrowest → broadest defined organism content: purified prebiotic substrate → single-strain probiotic → defined multi-strain consortium → undefined whole-community FMT (synthesised from G&G 14e Ch.6, pp.125–6).