4 - The microbiome

• Microorganisms ubiquitous in nature and found to be present on almost all our external and internal membranes
• Community composition differs at different body locations in a healthy human
• all internal and external surfaces are colonised by bacteria and are considered non-sterile
• actinobacteria are key part of the bacterial community composition of skin
• On skin and along facial mucosal membranes, firmicutes and acinobacteria dominate
• GI tract - bacteriodetes dominate instead
• Elie Metchinkoff did a study and modifying the gut flora with good bacteria. He hypothesised that consuming healthy bacteria could fight off harmful bacteria and prolong life.
• Commensal: an association between two organisms in which one benefits and the other derives neither benefit nor harm.
• Disruption of intestinal microbiota homeostasis is called dysbiosis
• The GIT and the intestinal microbiota display a symbiotic relationship.
• Two unrelated healthy individuals may have very different microbiomes
• Pathogenic bacteria such as pseudomonas, clostridum and colioform can be present in our microbiomes but as long as the proportion of them remain correct, the community is healthy, they dont cause harm.
• Balance is key - when the relative concentrations of bacteria are appropriate – we have symbiosis and no rise of pathogen members
• Firmicutes: gram +

  Lactobacillales - good bacteria

  Clostridia – C. diff is pathogenic, but there are others which are non pathogenic and an important part of balanced gut microflora.
• Bacteroidetes: gram –

  Bacteroides spp. (means many species)
• Actinobacteria: gram +

  Bifidobacteria spp.
• Proteobacteria: gram –

  E.coli and shigella – often implicated in pathogenesis – but they are often present in balance at low concentration and relative concentration is not causing harm

  Other species and variants like O157 H7 e. coli are harmful
• Fusobacteria gram –

  Fusobacterium spp.
• The Human Microbiome Project aims to characterise the microbiome. It has isolated and sequenced over 1,300 reference strains from the human body.
• It is very hard to define what is a healthy community due to the huge individual variability
• Initial feeding – milk – important because bacterial contact as well as immunity – IgA and IgGs in breast milk. Two different microbial communities in mothers milk or bottled milk.
• In utero there may be microorganisms in the amniotic fluid and placenta which transfer to the baby. This is theorised as the mercomium (the earliest stool produced by human babies, before any food consumed) contains bacteria sp. However most microbes are acquired post-partum.
• Mode of delivery affects the composition of bacteria.

  Vaginal birth: infant inoculated with vaginal microbiota; larger population of Bacteroidetes than Firmicutes compared to caesarean section

  Caesarean section: infant inoculated with skin microbiota
• The initial colonisation is important because these initial good bacteria are going to help outcompete others which could be pathogenic
• The initial colonisation is also chaotic as lost of species will try to accumulate so the community takes time to settle and niches to be occupied.
• Colonisation occurs in stages:

  Initially aerobic organisms: enterobacteria, staphylococci and streptococci

  Later anaerobes increase
• Breast milk is not sterile, it contains over 600 different species, including Bifidobacterium spp. which is essential to a healthy microbiome.
• Human milk contains quantities of indigestible oligosaccharides, these stimulate growth for Bifidobacterium spp. and other beneficial bacteria species which can digest them. This strengthens the gut mucosal protection against pathogens and increases production of immunoglobulin A.
• Breast-fed infants have lower concentrations of some pathogens such as Clostridia spp.
• Assembly of gut microbiome:

  Initial colonisation from firmicutes from breast milk.

  Proteobacteria develop small in relative abundance to firmicutes

  Fever promotes growth of certain bacteria i.e. E.coli like 39 rather than 37

  Weaning and table foods introduce Bacteroidetes, these out compete the initial firmicutes.
• Start life with relatively few species so the community is unstable
• Richness grows with time as does the stability - most stable in adulthood.
• As we age the microbiome becomes less stable with age.
• Ageing

  Relative proportions of Firmicutes predominating in the elderly compared to higher proportions of Actinobacteria & Proteobacteria in infants
• Alcohol effects the composition of the microbiome, abuse of alcohol can cause alcohol induced pathology. The microbiome is changed and dysbiosis disrupts the GI tract.
• Alcohol-fed mice demonstrated a decrease in the abundance of Bacteriodetes and Firmicutes and an increase in Proteobacteria and Actinobacteria.
• Pro-biotic supplementation prevented the dysbiosis that occurs in alcohol induced pathology.
• A number of diseases are associated with microbial dysbiosis
• Faecal Microbiota Transplantation (FMT)

  used to treat serious dysbiosis, such as with C.diff infection.(Both C.diff and antimicrobials may wipe out biota).

  After the FMT bacteria relative abundance can be re-established, by removing bad bacteria with antibiotics.
• obesity is associated with lower microbial diversity