Understanding the Microbiota

drawings of microbiota

 

What is the microbiota?

Thousands of years of coexistence have given rise to intricate relationships forming between animals and the microbes which live on or within them. This consortium of micro-organisms is made up mainly of bacteria, however 2% of the microbial DNA has been isolated from fungi,1 and protozoa, archaea and viruses are also known to be present. Together these micro-organisms form complex ecosystems, on or within the body, known as microbiota. While microbes have created ecosystems all over our bodies, we shall focus on the gastrointestinal (GI) microbiota, as this has been the subject of most research. There are estimated to be as many bacterial cells as there are human cells within the body,2 with the combined microbial genetic pool outnumbering the host gene content by a multiple of 100.3 Until fairly recently, bacterial culture was the only available method to identify bacterial species present within the intestinal microbiota. Given that only 20 percent of the intestinal bacteria are culturable,3 the numbers and species identified were hugely underestimated. The use of PCR amplification of 16S rRNA genes has enabled a more accurate insight into the bacterial populations present in the microbiota, and provides a way to investigate the microbial function via its gene content, known as the microbiome. Using this method, more than 2000 species of bacteria have been isolated from humans.4

The composition of the GI microbiota varies between individuals and between specific compartments of the gastrointestinal tract (GIT) within an individual.5 However, despite differing presence and abundance of specific microbes, it has been shown in dogs6 and people7 that the functional genetic content of the microbiota is conserved across individuals.

 

How does the microbiota become established?

Traditionally it was thought that the foetus developed in a sterile environment in the womb, with the first bacterial exposure occurring during birth. However, studies have demonstrated the presence of bacterial DNA in the placenta and amniotic fluid from healthy term pregnancies, not thought to be associated with intra-amniotic infection, and umbilical cord blood from neonates delivered by caesarean.8,9 Further to this, it has been shown that genetically labelled Enterococcus faecium given to pregnant mice, is found in the meconium of their pups, despite delivery by caesarean.10 Whilst live bacteria have not yet been identified, this does suggest some degree of in utero colonisation.

As they pass through the mother’s birth canal, infants are covered in vaginal and faecal microbes which contribute to the establishment of skin, oral, nasopharyngeal and gut microbiota. These infants acquire microbiota similar to that of the vagina, whereas infants born via caesarean develop a microbiota more similar to human skin.11 These differences in microbiota may result in long term health consequences to the child, in particular concerning immune-mediated disease. For example, children born via C-section are significantly more likely to develop allergic rhinitis, asthma, celiac disease, type 1 diabetes, and inflammatory bowel disease.12-15

Maternal microbial transmission continues beyond birth via breastfeeding. The mother’s milk contains hundreds of bacterial species16. Amongst some of the earliest species to be transmitted to the infant are Bifidobacterium longum subsp. infantis, which has been shown to have adaptations to promote milk utilisation.17

As the infant approaches weaning, the composition of the microbiota shifts to favour plant digestion. Unsurprisingly, introduction of varying food sources results in large changes to the microbiota.18 As dietary and environmental changes settle after the first few years of life, the established microbiota becomes fairly stable for that individual.19 Alterations may then occur following illness or infection, environmental or dietary change or exposure to certain medications, such as antibiotics.20,21

Since the blue-print of an individual’s microbiota is established in the first few years of life, alterations to the microbial populations during this time can have life-long effects on the host. For example administration of antibiotics early in life can alter the microbiota, which has been linked to an increased risk of obesity and allergies.21-23 It is proposed that excessive hygiene in childhood can affect the development of the microbiota and result in increased risk of allergies and inflammatory bowel disease later in life.24-26 This is known as the hygiene hypothesis.

 

What does the microbiota do and why do we need it?

We have discussed what the microbiota is and how it is established, but why is it so important?

A balanced microbiota is essential for host health in the following ways.

A healthy microbiota:

  • promotes normal gastrointestinal development. This is shown through the following examples, where the absence of a microbiota results in structural changes in the gastrointestinal tract. Antibiotic administration to rats at the end of gestation resulted in pups with small stomachs, reduced acid secretion and increased intestinal permeability.27 Germ free mice have been shown to have poor capillary development in the intestinal villi; however, this can be reversed by faecal microbial transplantation from mice with normal microbiota.28 Antibiotics given to pregnant sows resulted in altered intestinal architecture in their piglets.29
  • is involved in immune regulation. One of the most important roles of the microbiota is in the development of oral tolerance – the suppression of immune responses to harmless orally ingested antigens, and commensal bacteria. The dendritic cells present in the intestinal mucosa act to detect luminal contents including commensal bacteria, since these are harmless they stimulate creation of an anti-inflammatory environment.30
  • helps in defence against pathogenic organisms. This is not only by its close interaction with the immune system. The commensal bacteria also compete with pathogens for food sources and epithelial binding sites, and promote mucus production which creates a barrier between pathogenic bacteria and the gut epithelium.31
  • provides beneficial nutritional effects. By fermenting dietary substances, which are indigestible to the host, short-chain fatty acids are produced. These have many host benefits such as providing vital nutrition for enterocytes, modulating immune function and increasing mucosal blood flow.32,33
  • is involved in bile acid metabolism. Only gut bacteria can convert primary bile acids to secondary bile acids, the ratio between these is important in gut homeostasis. Alterations to bile acid metabolism may have negative health consequences. 34,35
  • is involved in the synthesis of certain vitamins. Gut microbiota can synthesize certain vitamins, notably Vitamin K and B group vitamins.36

 

What is dysbiosis?

Broadly defined, dysbiosis is any change to the composition of resident commensal microbial communities relative to the community found in healthy individuals.37 There may be a change in the species present or the abundance of each species present. Dysbiosis can be deleterious to the host as there may be an increase in pathogenic bacteria, which can be directly damaging to the host; or there may be a reduction in commensal bacteria, disrupting the normal functions of the microbiota as explained above. Dysbiosis may result in immune dysregulation, including reduced anti-inflammatory metabolites, and abnormal metabolism of dietary carbohydrates, bile acids and vitamins.

Dysbiosis has been described in dogs with inflammatory bowel disease (IBD) and acute diarrhoea, cats with chronic enteropathies, dogs and cats with Giardia duodenalis and dogs with meningoencephalomyelitis of unknown origin (MUO).38-45 In people dysbiosis is associated with a huge number of disease conditions, a few examples include: diarrhoea, IBD, IBS, obesity, colorectal cancer and diabetes.46-53

The involvement of the microbiota and dysbiosis in obesity is a hot-topic for research. One interesting study demonstrated that giving the microbiota from obese mice to germ free mice resulted in greater weight gain than when the microbiota from lean mice was given to germ free mice, despite being fed the same diet. On assessment of the microbiome, increased genes involved in energy extraction were found in the faeces from the obese mice.54

 

What are probiotics?

Probiotics help to support a healthy gut microbiomeand are defined by the World Health Organisation as “live microorganisms which when administered in adequate amounts confer a health benefit on the host”.55

 

What to check when looking for a probiotic:

A high quality probiotic product should state:

  • The organism(s) present, right down to the strain
  • The numbers of colonies present. (WHO recommends >1 x 109 CFU/kg)
  • The date by which the bacteria are guaranteed to be present at that level

 

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