Gut microbiota

The bacteria, fungi and archaea are part of our gut

Introducing the gut microbiota

The gut microbiota is the diverse microbial community found in our gut. In addition to bacteria, the gut microbiome is also made up of methanogenic archaea, dimorphic fungi and parasitic protozoa (figure 1) [1-4]. Even before birth we cultivate a complex community of microorganisms which change based on factors like our diet, age and genetics [3, 4, 5]. Out of the myraid of factors affecting the microbiota- antibiotics cause the most marked changes. In addition to eradicating enteric pathogens like Clostridium difficile, Enterohemorrhagic Escherichia coli (EHEC) and Salmonella enterica. Beneficial bacteria are also killed which destabilise the microbial community (dysbiosis) [5].

The gut microbiota digests indigestible carbohydrates such as cellulose and converts them into short chain fatty acids (SCFAs) via anaerobic respiration [1, 3, 4]. SCFAs like butyrate are thought to play important roles in colon health, however the butyrate paradox complicates this. In addition to aiding gut health through promoting terminal differentiation of colonocytes and reducing their proliferation. Butyrate also promotes proliferation of epithelial cells which in mice has been shown to promote colorectal cancer (CRC) tumour growth [5, 6].

Another beneficial secondary metabolites produced from the microbiota is tryptophan. Tryptophan is an essential amino acid as we lack a tryptophan synthase complex to produce the amino acid. In addition to being an essential amino acid; it is also a precursor of serotonin- an important neurotransmitter. Mice treated with antibiotics have been shown to have significantly lower levels of tryptophan in the blood highlighting this delicate relationship [7].

Microorganisms of the gut can be classified as symbiotic, commensal or pathogenic. Lactobacillus rhamnosus is a symbiont as it produces useful secondary metabolites like SCFAs and tryptophan promoting gut and neurological health. Commensal organisms like the yeast form of Candida albicans digest food that passes through the gut, but do not provide a direct benefit to us. Finally, gut microbes can be pathogenic (cause diseases) such as irritable bowel syndrome (IBS), inflammatory bowel disease and diarrhoea. One proliferic food-borne is the enteric pathogen is S. enterica.

Bacterial gut microbiota

Most bacteria of the gut microbiota are part of the gram-positive Firmicutes phylum and include the Lactobacillus genera. Lactobacillus species such as L. rhamnosus are suggested to improve neurological function and colon health through the production of SCFAs like butyrate [1, 7]. Other Firmicutes include C. difficile – a prolific opportunistic pathogen that can cause severe systemic C. difficile infections via enterotoxins [8].

The next most abundant phylum of the microbiota is Bacteroidetes [7]. Although commonly commensal; there are benefical species part of the phylum. For example, the anerobe Bacteroides .spp can help to reduce enteric infections and reduce dysmbiosis via its ability to digest gut mucosa glycans to support other species [9, 10]. Although, certain Bacteroides strains possess virulence factors and act as pathogens for diarrhoea [10].

Proteobacteria are significantly less abundant than the aforementioned Bacteroidetes and Firmicutes phyla. Despite being a smaller constituent of the microbiota. Despite being a smaller constituent of the gut than the aforementioned phyla. Nonetheless, Proteobacteria abundances have been used as a marker for dysbiosis (an unbalanced gut microbiota community) [11]. EHEC is one such Proteobacteria species part of the microbiota that produces shiga toxins to cause bloody diarrhoea [12].

Finally, Actinobacteria are a much smaller constituent of human microbiota [9]. This phylum includes Bifidobacterium species such as Bifidobacterium longum which produce indole that is beneficial for gut barrier function [13]. Additionally, increased prevalence of Bifidobacterium dentium has been associated with advanced age [14].

The fungal gut microbiota- the mycobiota

The mycobiota (fungal microbiota) is less characterised than the bacterial microbiota, but interest in this area is growing. Studying the mycobiota is more challenging as fungal internal transcribed spacer (ITS) 18S rRNA databases are not as well annotated as 16S rRNA bacterial databases- which can be it harder to distinguish species using metagenomics [15]. Additionally, some fungi like Candida albicans are dimorphic. Dimorphic fungi can convert between the unicellular yeast and multicellular hyphal forms which can add further complexity to sample annotations within the fungal databases [15]. Finally, using 18S sequencing to identify the fungal species requires pruning of other eukaryotic 18S rRNAs from protist, food and our tissues [15, 16]

Nevertheless, the main genera of the mycobiota are: Candida, Saccharomyces, Penicillium, Aspergillus and Malassezia. However, most mycobiota studies only identify Candida and Saccharomyces genera in samples [16, 17]. Although Saccharomyces species are commonly identified in the mycobiota, its presence is highly dependent on diet such as the consumption of bread [17].

The Candida genus is the most well-studied as it harbours the C. albicans species – the causative agent of intestinal candidiasis. Candidiasis is the process by which the yeast form of C. albicans converts into its virulent hyphal form which can spread uncontrollably resulting in deadly systemic infections [18]. Although there is far more research into the mechanism which triggers Candidiasis after bacterial dysbiosis. Carrying C. albicans may also have beneficial effects as it can promote immunoprotection from C. difficile and respiratory pathogens like Klebsiella pneumoniae [18].

Archaea and protists of the gut

The final set of organisms of the microbiome are Archaea and protists- which are not as well characterised as fungal and bacterial members of the microbiota.

Methanogenic dominate the archeal microbiota (archaeome) and produce methane as a metabolic byproduct of anaerobic respiration. Examples include species from the Euryarchaeota phylum- Methanobrevibacter smithii and Methanosphaera stadtmanae [19, 20]. These obligate anaerobes perform methanogenesis via a myriad of ways such as ultising H₂ to reduce CO₂into methane [19]. Non-methagenic archeal species also exist such as the halophilic Halorubrum alimentarium. Archea’s role in human health remains to be fully elucidated, but archaea overabundance has been associated with IBS, obesity and CRC [19].

Finally, eukaryotic protists are another constituent of the microbiota. The most prolific parasitic protist genera are from the: Blastocystis, Giardia and Cryptosporidium genera.

Around 1-2 billion people carry Blastocystis which can act as a commensal constituent of the microbiota. Although Blastocystis is commonly associated with disease (IBS, IBD and inflammation); there is evidence to suggest that the protist can promote bacterial diversity within the gut [21]. Comparatively, Giardia is a wholly pathogenic protist and is the causative agent of giardiasis. Giardiasis results in watery diarrhoea and promotes dysbiosis via disrupting the intestinal mucosa [22]. Finally, Cryptosporidium species like Cryptosporidium parvum disrupt the intestinal mucosa like Giardia and promote gut inflammation causing Cryptosporidiosis – a prevalent and deadly diarrheal disease [23].

The microbiota in summary

In summary, our gut microbiota hosts a wide range of microorganisms from beneficial Lactobillia to pathogenic Cryptosporidium. These organisms interact with our colonocytes in a myriad of ways from producing secondary metabolites from indigestible carbohydrates, digesting mucosal glycans both to promote colonisation of beneficial bacteria and cause disease. The microbiota’s effects on our health also extend outside of the gut with secondary metabolites affecting neurological function such as the production of tryptophan- an important and essential amino acid.