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.