Why differences matter more than similarities

I have reams of info on differences between pig, human and non-human-primate (NHP) gut microbiomes and their associated tissues, but don't have time to edit it for posting yet (could be some time...)

So I will have to settle for a few crucial extracts.

Why are you only focusing on the differences?

When an animal model (e.g. a pig) is required to provide scientific data on how processes occur in humans, its usefulness cannot be gauged by averaging the similarities and differences. If there are numerous relevant differences, the model is simply not representative, and will not give relevant answers, regardless of how many similarities there are.

If we want to find out which gut microorganisms cause which changes in the human immune system, and the pig gut wall does not respond in the same way as a human gut wall to a particular collection of gut flora (because of the different evolutionary histories/phylogenies of the two species), we will get the wrong answers, however many individual similarities we can identify. The differences will negate the similarities, even if there are numerically more similarities than differences.

Biochemistry involves a complex web of interactions. Just one missing or different component (e.g. an enzyme or receptor) can make an enormous difference to the whole. If you put the wrong fuel in your car, it is likely to malfunction, even if everything else is right. If you put an incorrect part in a computer, it is likely to malfunction even if everything else is right. If you use the wrong blood type in a blood transfusion, it can have fatal consequences, even if it has almost all the same components as the recipient's blood.

But results from animal models sometimes agree with results in humans, don't they?

Yes, they sometimes do. But we can't know this until we finally test in humans. Tossing a coin would also sometimes give us results that agree, and sometimes not. Animal models are, on average, no better than coin-tossing at predicting outcomes in humans.


On non-human primates as 'models' for humans

Won't using non-human primates overcome the problems of species differences?

No, because differences are still substantial, even between humans and our closest relatives, chimpanzees (I have specific info on chimp-human differences which I hope to post later).

A 2010 scientific paper here states:
Comparison of fecal microbiota from non-human primates with microbiota of human stool samples obtained in previous studies revealed that the gut microbiota of these primates are distinct and reflect host phylogeny.
Phylogeny = evolutionary history - see http://www.biology-online.org/dictionary/Phylogeny.

It is a near-certainty that, as when other species are used as hosts for human microbiota, the interfaces between the microbiota and the gut wall will also be sufficiently different in different primates for the effects of a given microbiota to be different.

Thus biochemical interactions between the donor microbiota and the host immune system will differ from those seen in humans. The presence or predominance of one type of gut flora may cause 'leaky gut' and/or pathological immune reactions in one mammal species but not another. There is no good reason to suppose that reactions will be the same in different species, as has been shown time and again with drugs, for example.

Evolution is a long, slow process, and cannot be brought about by implanting the microbiota of one species into another! It will not turn a mouse, a pig or a chimp into a human being, or create a human immune system. Look at what happens when you put the wrong fuel in your car, or the wrong blood into a transfusion patient.

The authors of the aforementioned paper go on to state:
...human subjects, like the NHP (non-human primate) species, showed high within-species similarity and clustered together, indicating that human fecal microbiota are distinct from those of other primates.
Our results provide compelling evidence that, in addition to diet, primate gastrointestinal microbiomes are functionally linked to their vertebrate host taxa, and are perhaps species-specific or population-specific...the fact that all subjects originated from the same location (Kibale National Park, Uganda) strengthens our conclusion that primate microbiomes are host-specific, in that differences in microbiomes observed among species cannot be accounted for solely by habitat differences.
...we have demonstrated that the microbiomes of three NHP species and of humans show a much higher similarity within the same primate species than among different primate species, even when habitats overlap between NHP species. This surprising degree of host-specificity might suggest that patterns of primate evolution may have influenced the structure of primate microbiomes...
A microbiome - or other aspect of a living system - does not, and cannot, evolve in isolation. Other tissues, structures, organs and biochemistry have to evolve along with them, otherwise they will not function correctly.

Whilst it is undeniable that different mammal species share some of the same microbiota, they are in different proportions, and mammal species also have microbiota which are not found in different mammal species. Thus the overall community/population of gut flora is different.

Just as most individual food types are not inherently harmful, some are to some people/some mammal species (e.g. xylitol is poisonous to dogs, and peanuts can be fatal if ingested by some people). But it is generally the overall composition/balance of the diet, and the overall composition/balance of the microbiota, which is beneficial or harmful to a given mammal species/human being.

Comments

A good logical and well argued point of view and which makes a lot of sense. Tiny differences can make a very big difference and particularly when evolution works on those differences over millions of years.

Regards.
 

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