The human colon is colonised by microbes that can utilise both inorganic and organic sources of sulphur. The inorganic pathway are the so-called sulphate reducing bacteria and they mostly use hydrogen gas, which is a by-product of fermentation, as a source of electrons to reduce inorganic sulphate to sulphide, hydrogen sulphide, a genotoxic and pro-inflammatory gas that’s made by those organisms that use inorganic. There are also other microbes that can utilise organic sources of sulphur such as the amino acids taurine and cysteine. One in particular that we’re very interested in and have done a lot of work with is Bilophila wadsworthia, that’s a bacterium that respires taurine through a three enzymatic step. It can also generate hydrogen sulphide as an endpoint in that metabolic pathway. Then other organisms can use cysteine, so it’s a fermentative process that also generates hydrogen sulphide.
How does this lead to colorectal cancer?
We’ve demonstrated that hydrogen sulphide at concentrations lower than have been measured in the human colon, exogenous hydrogen sulphide, is a potent genotoxin so it induces DNA damage directly and is also pro-inflammatory and a pro-inflammatory environment is a predisposition to colorectal cancer. So that’s the work we’re pursuing.
Does this lead to colorectal cancer?
Certainly, but more importantly and more innocuous would be diet. The work we’ve done also demonstrates that an animal-based diet promotes the growth of these organisms, particularly those that utilise organic sources of sulphur which would be increased in an animal-based diet that’s high in both protein and fat. So the application of the work we’re doing is perhaps the relative abundance of this organism that uses taurine, as an example. It could be a biomarker that one could then advise the individual based on the relative abundance of this organism that uses taurine, which would be increased in a diet high in animal products, to very carefully watch the diet.
By going vegetarian?
Well yes, everything in moderation. So it’s processed meat. The amount of taurocholic acid, it’s one of the primary bile acids, is increased with a diet high in animal fat and the taurine can be cleaved from taurocholic acid which can then be used as a substrate for this microbe that we’ve demonstrated is persistently colonising the mucosa, tightly adherent to the mucosa, where it would have contact with the colonocytes.
Do you think this is influenced by the western diet?
It could be and there have been studies. So we’ve also done a study with native Zulu Africans, for example, and their native diet for the traditional Zulu is a maize based porridge, phuthu, and they grind the corn in the morning and make a porridge that’s flavoured with root crops. That’s what they eat throughout the day and that’s very high in fibre, resistant starch precisely. So it’s a highly fermentable diet and the instance of colorectal cancer, for example, is essentially nil in the traditional Zulu population. So we did a study that compared, we did a diet swap with Zulu Africans and African Americans which in the US consume a high meat-based diet. We had twenty Zulu Africans and twenty African Americans and we switched the diets so we fed the African Americans the phuthu for two weeks and we fed the Zulu Africans an extreme Western diet for two weeks and we had biopsies before and after the diet swap. We saw increases in the abundance of these bacteria that make hydrogen sulphide in the Zulu Africans that were fed the animal-based diet for two weeks and we also saw corresponding changes in host biomarkers of colorectal cancer risk.