Wednesday, 13 November 2013

Updating the human gut microbiome to degrade seaweed

The microbial community of the human gut possess “carbohydrate active enzymes”, or CAZymes, that are absent from the human genome. These CAZymes are used to digest and metabolise polysaccharides that our own enzymes are incapable of affecting.  Metagenomic analyses of the gut microbiomes of American, Spanish and Japanese populations has shown the presence of CAZymes from marine bacteria, obtained via horizontal gene transfer, that confer the ability to digest algal polysaccharides such as those found in sushi.

Before this study, it was already known that the two major phyla in the gut community are the Firmicutes and the Bacteroidetes, and that the majority of their enzyme systems are devoted to the breakdown of host glycans and the terrestrial plant material that makes up the majority of the human diet. What remained unknown, or at least required more evidence before an evaluation could be made with any degree of certainty, was how the microbial gut community evolves to process new sources of carbohydrate.

The authors have provided this evidence, by establishing how a horizontally acquired integrative and conjugative element (ICE) was able to confer Bacteroides plebeius with the ability to metabolise the red seaweed polysaccharide porphyran. They were able to show via X-ray crystallographic and biochemical analysis that the obtained ‘polysaccharide utilization locus’ (PUL) consisted of 40 genes coding for proteins that included β-porphyranases. Growth experiments showed that B. plebeius was able to utilise the PUL to grow on the porphyran, whilst it could not grow on similar carbohydrates such as agarose and carrageenan. Transcriptomics showed that the genes of the PUL were upregulated when the bacterium was grown on porphyran. They also identified two other gut Bacteroides, B. uniformis NP1 and B. thetaiotaomicron VPI-3731, that were able to grow on agar and carrageenan, which contrasted with previous studies suggesting that such metabolic pathways were absent from the gut microbes.

Some of the enzyme-coding genes on the PUL were shown to be expressed even in the absence of their polysaccharide substrate, in what the authors dub ‘surveillance’ levels.  This is common in Bacteroides, the production of small amounts of an enzyme to initially recognise and breakdown a polysaccharide which then triggers upregulation of that enzyme. A similar process occurs in the lac operon of other enteric bacteria.

The findings of this study are likely to have health implications, as red algae galactans (a class of polysaccharides including carrageenans, agars and porphyrans) are known to have a range of pharmacological effects. Health concerns have been associated with the products of carrageenan catabolism, as they have been shown to cause ulcerative colitis in animal trials. B. thetaiotaomicron VPI-3731 showed strong growth on carrageenan, inferring it must carrageenases and be capable of producing these harmful products. Further research would be required to discern if their presence in the gut microbiome has detrimental effects on the host. However, red algae galactans are also known to have antiviral, anticancer, anti-inflammatory and anti-oxidative effects, so many of the microbes catabolising them in the gut are likely to have a beneficial effect on their host.

This is purely speculative however. The main finding from this paper supports the hypothesis that the gut microbiome coevolves with host diet through horizontal gene transfer from extrinsic microbes enabling the catabolism of new carbohydrates.  

Hehemann, J. H., Kelly, A. G., Pudlo, N. A., Martens, E. C., & Boraston, A. B. (2012). Bacteria of the human gut microbiome catabolize red seaweed glycans with carbohydrate-active enzyme updates from extrinsic microbes. Proceedings of the National Academy of Sciences, 109(48), 19786-19791.


  1. An interesting follow up study would be to trace these genes back to the marine bacteria that gifted CAZymes to human gut microbes. I wonder if these marine bacteria use 'surveillance' levels of expression also; it seems like a good adaptation for a copiotroph to have (no point in making a digestive enzyme until the right substrate comes along), so it seems odd for microbes living in the nutrient rich human gut to have it. I also wonder how prevalent CAZyme genes are amongst marine taxa compared to gut taxa, given that horizontal gene transfer rates and selective pressures in the gut are likely very different.

    1. Yes I was hoping they would trace the genes back, but unfortunately not, I guess they would have to search a database to see in which other bacteria the genes are found, then try to limit those to the ones likely to come into contact with our gut flora, i.e. those we might consume. I imagine most if not all operons use a surveillance level of expression, it is required to recognise the presence of the substrate and to initiate further enzyme production, they are unlikely to remain 'switched off' all together. CAZyme is an umbrella term for any enzyme that degrades, modifies or constructs glycosidic bonds in carbohydrates, so I imagine they are prevalent in all heterotrophs for catabolism, and all life for anabolism.

  2. Hi Dave,
    Thank you for summarising this study! I have actually read the paper which was published a couple of years previous to the one you have summarised for my dissertation; "Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota" (Hehemann et al., 2010), where they tried to find out where the gut bacterium Bacteroides plebeius got the genes coding for the enzymes from. They isolated the bacterium Zobellia galactanivorans from a red alga Delesseria sanguinea as this bacterium is known to be able to degrade agars and carrageenans. Their methodology was fairly complex in terms of how they came to their final conclusions and it took me a bit to get my head around it. Anyway, they found evidence that B. plebeius acquired a porphyran utilisation locus that originated from an ancestral porphyranolytic marine bacterium which is related to the marine Bacteroidetes Z. galactanivorans and also Microscilla sp. PRE1.
    I find it interesting that they have identified two other species that are able to grow on agar and carrageenan; I wonder how many other gut Bacteroides sp. are yet to be identified to be capable of this. It’s hard to imagine that it’s only these three species.

    1. It is hard to imagine, there is probably a large diversity, but culturing techniques etc must limit the ones we find.
      I wonder how this research relates to the Orkney Island sheep mentioned in today's marine living resources lecture (do you do that module?) Perhaps they have a similar diversity, or probably a greater diversity considering seaweed makes up most of their diet.
      Ha, the fact that it received its porphyrase genes from a 'porphyranolytic bacterium' kind of removes the mystery, I could have made that up myself.
      What a coincidence that you have read the original paper for your lit review, what is your dissertation on?

  3. I don't do that module unfortunately, but may be I should come to the lectures in the future, it sounds pretty cool!
    My project is about analysing the microbial community in rocky shore biofilms and the microflora of limpet guts that feed on the biofilms and try to see how the microflora relates to what is found in the biofilms; so I cover a lot about how the type of diet can shape and influence the organism. The CAZyme paper was one of the first ones I read, although it deals with a bacterium in the human gut. :)