''Phocaeicola plebeius'', formerly ''Bacteroides plebeius'', is a

microbe A microorganism, or microbe, is an organism of microscopic size, which may exist in its single-celled form or as a colony of cells. The possible existence of unseen microbial life was suspected from antiquity, with an early attestation in ...

found in the human gut, most commonly in Japan natives. It is able to digest

porphyran Porphyran is a sulfated carbohydrate derived from red algae of the genus ''Porphyra''. Composition Porphyran is a complex sulfated carbohydrate. It is a highly substituted complex carbohydrate related to agarose with a linear backbone consisting ...

, a polysacchide from ''

Porphyra ''Porphyra'' is a genus of coldwater seaweeds that grow in cold, shallow seawater. More specifically, it belongs to red algae phylum of laver species (from which comes laverbread), comprising approximately 70 species.Brodie, J.A. and Irvine, L ...

'' seaweed (

nori Nori is a dried edible seaweed used in Japanese cuisine, usually made from species of the red algae genus ''Pyropia'', including ''P. yezoensis'' and ''Pyropia tenera, P. tenera''. It has a strong and distinctive flavor, and is generally made in ...

) that humans cannot digest on their own. The porphyranase-encoding gene Bp1689 is believed to have been derived from the microbe '' Zobellia galactanivorans'' via

horizontal gene transfer Horizontal gene transfer (HGT) or lateral gene transfer (LGT) is the movement of genetic material between organisms other than by the ("vertical") transmission of DNA from parent to offspring (reproduction). HGT is an important factor in the e ...

, as part of a

gene cluster A gene cluster is a group of two or more genes found within an organism's DNA that encode similar peptide, polypeptides or proteins which collectively share a generalized function and are often located within a few thousand base pairs of each othe ...

containing other

carbohydrate-active enzymes CAZy is a database of Carbohydrate-Active enZYmes (CAZymes). The database contains a classification and associated information about enzymes involved in the synthesis, metabolism, and recognition of complex carbohydrates, i.e. disaccharides, oli ...

Composition of red algae ''Porphyra''

'' is a genus of red seaweed. The two main ''Porphyra'' used in Japanese dishes are '' P. yezoensis'' and '' P. tenera'' which are commonly used in

sushi is a traditional Japanese dish made with , typically seasoned with sugar and salt, and combined with a variety of , such as seafood, vegetables, or meat: raw seafood is the most common, although some may be cooked. While sushi comes in n ...

. ''Porphyra spp.'' also known as

in Japan contains compounds such porphyrans and

agarose Agarose is a heteropolysaccharide, generally extracted from certain red algae. It is a linear polymer made up of the repeating unit of agarobiose, which is a disaccharide made up of D-galactose and 3,6-anhydro-L-galactopyranose. Agarose is on ...

s that are indigestible to people lacking ''P. plebius''.

Rhodophyta Red algae, or Rhodophyta (, ; ), make up one of the oldest groups of eukaryotic algae. The Rhodophyta comprises one of the largest phyla of algae, containing over 7,000 recognized species within over 900 genera amidst ongoing taxonomic revisions. ...

, the phylum of red algae, has a

cell wall A cell wall is a structural layer that surrounds some Cell type, cell types, found immediately outside the cell membrane. It can be tough, flexible, and sometimes rigid. Primarily, it provides the cell with structural support, shape, protection, ...

composed of

sulfate The sulfate or sulphate ion is a polyatomic anion with the empirical formula . Salts, acid derivatives, and peroxides of sulfate are widely used in industry. Sulfates occur widely in everyday life. Sulfates are salts of sulfuric acid and many ...

galactan Galactan (galactosan) is a polysaccharide consisting of polymerized galactose. In general, galactans in natural sources contain a core of galactose units connected by α(1→3) or α(1→6), with structures containing other monosaccharides as sid ...

s. Agarans, a main component of the cell wall is composed of alternating 3-linked β-D-galactose and 4-linked α-L-galactose. Porphyran is a water-soluble agaran found in ''Porphyra''. The porphyran backbone is composed of roughly 30% 3-linked β-D-galactose and 4-linked 3,6-anhydro-α-L-galactose. The remaining 70% is composed of 4-linked α-L-galactopyranose-6-sulfate or 3-linked β-D-galactopyranose.

Horizontal gene transfer

''P. plebeius'' is believed to have acquired a cluster of sugar-processing enzymes from ''Z. galactanivorans'', a marine bacterium. The two most important transferred genes are Bp1689 ( GH16 β-porphyranase) and Bp1670 (GH16 agarase), as the

enzymes An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as pro ...

they make deal with sugars found in the molecule. (Other transferred genes, such as two GH86 aragases, a sulfatase, and various regulatory parts, play a role too.) Specifically, Bp1689 hydrolyzes the (1→4) linkage between β-D-galactopyranose and α-L-galactopyranose-6-sulfate in porphyran. Structurally it contains a

TIM barrel The TIM barrel (triose-phosphate isomerase), also known as an alpha/beta barrel, is a conserved protein fold consisting of eight alpha helices (α-helices) and eight parallel beta strands (β-strands) that alternate along the peptide backbone. ...

domain and two

β-sandwich Beta-sandwich or β-sandwich domains consisting of 80 to 350 amino acids occur commonly in proteins. They are characterized by two opposing antiparallel beta sheets (β-sheets). The number of strands found in such domains may differ from one prote ...

domains. A number of other genes are also transferred with Bp1689 and Bp1670. In total, 11 genes are believed to have been transferred: they do not occur in other ''Phocaeicola'' species (known as of 2010) and have sequence similarity of 48%-69% compared to

ortholog Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a speci ...

s in ''Z. galactanivorans''. Moreover, transferred genes in both species are located in similar orders along their chromosome (i.e. they are syntenic). There are also genes related to the HGT in these 11. In 2012, it was reported that ''

Bacteroides thetaiotaomicron ''Bacteroides thetaiotaomicron'' is a Gram-negative, obligate anaerobic bacterium and a prominent member of the human gut microbiota, particularly within the large intestine. ''B. thetaiotaomicron'' belongs to the ''Bacteroides'' genus – a gro ...

'' VPI-5482 has a related set of genes in the same order, albeit specialized to a different task: degradation of α-mannan, a fungal sugar. Discovery of this more intact cluster further confirms the role of HGT. A different nomenclature of these genes use the gene family instead of chromosomal sequence numbers. In this scheme, Bp1689 is BpGH16B and Bp1670 is BpGH16A.

Impact on colon cancer

A recent study in mice showed that gut colonization by ''P. plebeius'' can suppress colitis-associated colon cancer, especially when combined with a seaweed diet. Mice colonized with ''P. plebeius'' and fed seaweed had reduced inflammation and fewer, smaller tumors. The study found that ''P. plebeius'' altered the gut microbiota, increasing abundance of bacteria with anti-inflammatory effects. This was accompanied by downregulation of

cytokines Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

and other immune-related genes, such as

chemokines Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In addit ...

. Some genes, including ''Spta1'', ''Malrd1'', ''Six2'', and ''Ugy2b5'', were upregulated, though their connection to tumor development is still unclear. The mechanism by which ''P. plebeius'' affects host gene expression is unknown, but may involve microbial

metabolites In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

. Another mechanism of tumor suppression may relate to

fucose Fucose is a hexose deoxy sugar with the chemical formula C6H12O5. It is found on ''N''-linked glycans on the mammalian, insect and plant cell surface. Fucose is the fundamental sub-unit of the seaweed polysaccharide fucoidan. The α(1→3) l ...

, a sugar that increases during colon cancer and promotes tumor growth. ''P. plebeius'' produces α-fucosidase, an enzyme that breaks down fucose, potentially reducing its concentration in the gut and limiting its tumor-promoting effects.

References

External links

Type strain of ''Bacteroides plebeius'' at Bac''Dive'' - the Bacterial Diversity Metadatabase
{{Taxonbar, from=Q25840254 Bacteroidia Gut flora bacteria Bacteria described in 2005