We Are What We Eat: The "Sushi" Gene

Author: Edoardo Moccia
Date: 09/12/2013



Imagine that you have in front of you a food that belongs to a different culture and a nation, it can be tempting, but the aromas and flavors unknown to us makes we pose the question: "Can I digest it?".
Why this question?
The people belonging to the particular culture of that food can digest it without any problems, why we should not do that?
The question really is well justified.

The Importance of the Diet

The human genome has fewer genes that encode enzymes capable of degrading plant polysaccharides and then the dietary fiber found in whole fruits and vegetables. Therefore these nutrients arriving in the distal portion of the intestine, where hundreds of microbial species are able to degrade these fibers and free sugars of the correct size to be used. The set of microbial species constitutes the intestinal microflora; this is different from individual to individual and, in particular, is affected by our diet.

There are differences both between herbivores, carnivores and omnivores, but also between different cuisines, with the typical foods of each nation. So, for example, there will be substantial differences between the microflora of an individual Italian and a Japanese.

Within the intestinal microflora is a fierce competition when they get the nutrients. A possible strategy for the intestinal microorganisms is to acquire a higher efficiency, compared to other competing species, adding to the kit further genes capable of synthesizing enzymes to digest an increasing number of foods.

The manner by which a bacterium is able to obtain new genes is said horizontal gene transfer. The new gene (and therefore the new enzyme) can gives bacteria a distinct advantage over the other members of the community, for example, if the bacterium is the only able to degrade a given fiber, it will occupy a more prominent place in the ecosystem.
In particular, this work aims at finding the reasons and differences in intestinal microflora of eastern populations, adept at digesting raw fish, in contrast with western populations that they have not a favorable digestion.

The Japanese case

Japanese cuisine is particularly rich in algae. These marine plants, including green algae, red and brown produce polysaccharides that have no equivalent in land plants.
In many bacteria associated with marine living algae, and among these organisms , there are samples of the degradation of the algae’s fibers. (Wikipedia)

For further information concerning the correlation between the intestinal microflora and dieta, read A genetic gift for sushi eaters, April 2010

Zobellia galactanivorans and his new Enzymes Class

The Zobellia galactanivorans, a marine flavobacterium isolated from the surface of the red Delesseria sanguinea, is the perfect model for understanding the specific metabolic pathways of the bacterium in the marine environment.
Knowing the complete genome, and studying the diversity of specialized enzymes in the degradation of the polysaccharides of the algae made by Z. galactanivorans, has identified a new class of enzymes, which are present mainly in edible algae of the genus Porphyra: the porphyranases.

Once we know this new activity, curiosity led us to search for other porphyranases in different environments. In fact, scientists now have at their disposal the necessary techniques to explore the composition, diversity and the redesign of microbial communities within an ecosystem . These techniques are based on large-scale sequencing of DNA present in a given environment, for example the intestinal microflora.

Thus, this revolutionary method (called metagenomics), applied to the analysis of the microflora of 13 volunteers and 18 Japanese Americans, has allowed us to identify the genes of the vast majority of the bacteria that live in the intestines of these individuals.
This set of genes is called microbiome.

The porphyranases genes are not existing in marine bacteria, with the exception of a bacterium isolated from the intestinal microflora of a Japanese individual, the Bacteroides plebeius. And the comparison of the Japanese microbiome with the American one has confirmed this: in Japanese microbiomes we identified six genes that encode porphyranases in six different individuals, while in micorbioma Americans we have not found anyone!
This exclusive distribution proved to be statistically significant. Now we have just to understand the origin of these genes exotic.

For further information concerning Zobellia galactanivorans and the porphyranases, read Le transfert de gènes du milieu marin vers la microflore intestinale chez les Japonais, October 2010

Bacteroides plebeius: How it Works

B. plebeius a bacterium is able to synthesize a large enzyme, said PUL, that has an amino acid sequence very similar to that of the enzymes of microbes seaweed and these activities have on porphyran. This finding supports the hypothesis that the PUL enzyme has been acquired by a marine bacterium and suggests that agarose, carrageenan or porphyran can be nutrients for this microbe. Following research it is seen that not only the preferred substrate is porphyran but that the same substrate active most of the genes leading to the synthesis of the enzyme degrading. The synthesis of this enzyme mobilizes 40 genes that produce among other things 12 glycoside hydrolase and a two-component system that sensory capacity and adjustment, it is also seen that RteA and RteB are important to start the excision and mobilization of conjugative transposons that carry genes for resistance to antibiotics.

For further information concerning Bacteroides Plebeius, read Bacteria of the human gut microbiome catabolize red seaweed glycans with carbohydrate-active enzyme updates from extrinsic microbes, November 2012

The Horizontal Gene Transfer

By analyzing the genome of Bacteroides plebeius, we can notice that the porphyranase gene, and the 10 genes which surrounds this one, are very similar to the genes identified in marine bacteria, and were not present in the genomes of other intestinal Bacteroides species .
Therefore, our analyzes revealed transfer of genes from a marine bacterium ancestral and specific intestinal bacteria of Japanese!
Interspersed between the genes shared with marine bacteria, there are genes well conserved with other gut Bacteroides, showing that B. plebeius is a regular gut symbiont that received an unusual set of genes most probably by horizontal gene transfer (HGT) from a marine bacterium.
The possible mechanism for HGT was identified by analysing the region downstream of Bp1670, which contains genes coding for conserved relaxase/mobilization proteins (Bp1662 and Bp1663/Bp1665), required for conjugative DNA transfer21.

In conclusion, these results indicate that B. plebeius acquired a porphyran utilization locus that originated from an ancestral porphyranolytic marine bacterium, related to the extant marine Bacteroidetes Z. galactanivorans.

In contrast, when analysing the gut metagenome data of 18 North American individuals, no porphyranase or agarase genes were detected.
Altogether, analyses of the available genomic and metagenomic data indicate that porphyranase and agarase genes are specifically encountered in Japanese gut bacteria and are probably absent in the microbiome of western individuals.
The detection of this HGT was possible owing to two favourable factors: b-porphyranases are absent in terrestrial microbes, and the transfer was relatively recent compared to the millions of years of mammalian gut microbiome evolution. This is supported by the high sequence identity of the porphyranase and associated genes in B. plebeius with genes found in marine Bacteroidetes. In contrast, acquisition of terrestrial plant-specific CAZyme genes probably occurred early in the evolution of herbivorous/omnivorous mammals, and such horizontally acquired genes would be difficult to distinguish from ancestral, vertically transmitted genes. The timing of such a HGT event is, however, difficult to estimate.

But…why the genes described here were acquired by Japanese gut bacteria?
Tax records from the eighth century list seaweeds as payments to the Japanese government, showing that they had an important role in Japanese culture. Dietary seaweed therefore is the most probable vector for the contact with marine microbes that led to HGT, as the only porphyran source in human nutrition is nori.
Traditionally, nori is not roasted and thus contact with associated marine microbes is promoted through Japanese sushi. Consequently, the consumption of food with associated environmental bacteria is the most likely mechanism that promoted this CAZyme update into the human gut microbe.
This hypothesis is more plausible that the algae, especially those of the genus Porphyra (nori) (Wikipedia ), are an important basis for nutrition and the culinary culture of the Japanese, and for at least 1,000 years. Once ingested by the Japanese, these bacteria associated with marine algae were able to come into contact with intestinal bacteria and transfer them to their "tools."

For further information concerning the horizontal gene transfer and Zobellia galactanivorans, read Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota, February 2010

Conclusions: the “sushi factor”

Our intestinal bacteria would be able to acquire the same intestinal bacteria of a Japanese if we ate regular meals made from raw algae? The question that comes to mind is open.
However, the gene transfer between bacteria and intestinal bacteria environment have occurred during the evolution of vertebrates, and so it explains the prevalence of polysaccharide-degrading enzymes of land plants in the microflora of herbivores and omnivores.

This discovery of the "sushi factor" is, in any case, the only beginning of a broader scope investigation of the evolution of human microflora.

Andrea Cortona, Edoardo Moccia
CdL in Odontoiatria e Protesi Dentaria

2013-12-10T13:54:48 - Edoardo Moccia
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