genetics

 A poor evolutionary nutrition narraive posits that because we didn't have X food in the paleolithic, we are maladapted to it. I think Mat Lalonde covered issues with this nicely at AHS and in the latest Paleo Solution podcast. 

Here is a funny twist to the story if it turns out to be true:

John Hawks, a biological anthropologist at the University of Wisconsin-Madison, notes that many HLA genes pre-date humans' split from Neanderthals and Denisovans, and that the differences may have arisen by chance as the groups evolved.

Hawks, too, has been digging into the archaic genomes, and his team has already discovered that Neanderthals and Denisovans lack certain forms of genes that may help modern humans to fend off epidemic diseases, such as measles. This is hardly surprising: the low population density of hunter-gatherers meant that epidemics were unlikely, so they probably would not have benefited from these immune genes.

But Hawks's team is now using the find to test whether the defensive genes are linked to autoimmune diseases. In September, Hawks and his colleague Aaron Sams are scheduled to present data at a meeting of the European Society for the Study of Human Evolution in Leipzig, Germany, showing that the Denisovans lacked nearly all of the gene variants linked to coeliac disease, a gut autoimmune disorder present in modern humans. Hawks suspects that the variants may actually be in the same genes that are linked to epidemic resistance — if they are, further study could reveal how recently such autoimmune diseases arose in humans.

Haha, it would be funny if an adaptation to civilization (diseases worsened by high population density), would also turn out to be a maladaptation as civilization progressed. 

A thought provoking book about the possibility that human cultures co-evolved with certain foods.

 The fact that humans cannot digest certain fibers and starches in the diet does not mean they are nothing but bulking matter. In the scientific world, more and more research focus has been on the fact that these seemingly indigestible ingredients actually are often digested in the human body, just not by human enzymes. Instead, they are digested by human gut bacteria.

While the human gut may not rely on its bacterial population for calories to the extent that other primates do, the colonic microbiome remains of vital importance to human health. Scientists are just discovering how the bacterial population and its byproducts play important roles in human nutrition, the immune system, and other vital bodily processes. The gut flora is currently under investigation for its role on hundreds of diseases (Guarner & Malagelada, 2003).

Borne out of this are several new paradigms for studying fiber, not as bulk, but as an interaction agent with gut bacteria. The importance of the species mix, population level, and products has been emphasized. One new term for some fibers is “prebiotic.” A prebiotic fiber is indigestible by human enzymes, but stimulates the growth of certain beneficial gut bacteria such as Bifidobacterium and Lactobactillus (Gibson, Roberfroid, & Louuain, 1995). Among the most effective are fructooligosaccharides such as inulin. These are present in modern foods such as Jerusalem artichoke, chicory, onions, and garlic, but there is extensive evidence inulin-rich foods were eaten in the Paleolithic (Henry, Brooks, & Piperno, 2010; Leach & Sobolik, 2010).

More interestingly, prebiotics are a component of human breast milk as human milk oligosaccharides (HMO), which play an important role in establishing gut bacteria that modulate the immune system (Bode, 2009). They are currently not added to infant formulas and deficiency in them has been linked to diseases such as necrotizing enterocolitis.

Figure 1: HMOs help protect the infant from infections through reducing the ability of pathogens to bind gut cells.

All primates produce milk oligosaccharides, but HMOs differ structurally from those of chimpanzees and bonobos (Urashima et al., 2009). These differences could stem from disease pressures, but since HMOs are important for establishing gut bacteria, it is possible they also evolved to set up the optimal bacterial mix for each primate’s diet and environment. There have been few studies on the differences between different primate gut microflora, but the few available such as an analysis comparing macaques and humans suggest that the human gut microflora is significantly different (McKenna et al., 2008).

Gut flora comparison

Where these species come from is a controversial matter. Studies trying to use orally administered probiotics have failed to establish these prebiotic bacteria in the gut, though implanting feces from healthy donors through enemas (bacteriotherapy) has been found to re-establish the flora of some desperately ill individuals (Khoruts, Dicksved, J. K. Jansson, & Sadowsky, 2010; Tuohy, 2003). Evidence points to most gut bacteria being established through maternal transfer (Ley, Peterson, & Gordon, 2006). Most of the gut bacteria cannot be survive outside the gut, so it is likely they have been our residents for a very long time. Analyzing the roles of various bacteria and trying to determine how long they have been residents in hominid guts is a potential method for analyzing diets of our ancestors.

It also calls into question the origin of gut microbiota differences in human populations. A study of gut bacteria comparing rural children from Burkina Faso to urban children in Italy found that during breastfeeding their gut ecology was not significantly different (De Filippo et al., 2010). However, once they started eating solid foods, their gut bacterial populations differentiated.

Figure 3 rRNA analysis of gut bacteria from chidlren from Burkina Faso and Italy

Children from Burkina Faso had greater levels of Bacteroidetes and lower levels of Firmicutes. Their microbiota contained bacteria from the genuses Prevotella and Xylanibacter, completely absent from the Italian children. The bacteria are known to contain a set of genes for cellulose and xylan hydrolysis, so it is possible they are selected for in the gut due to the high levels of these fibers in the Burkina Fasan diet. It would be interesting to know whether or not these bacteria represent an ancestral condition in humans that was lost in populations with less reliance on fiber. The Italian children also had more bacteria associated with disease, perhaps a relic of urbanizations effects on increased pathogen transmission.

It is not just the species that matter, but genetic variation within species of bacteria. A recent study showed that gut bacteria may obtain genes relating to food digestion from bacteria present in food. Analysis of bacteria from sixteen people found that a gene for producing porphyranases, enzymes used to digest porphyrans, a carbohydrate type only found in seaweed, were only found in Japanese individuals (Hehemann et al., 2010). The only other place porphyranase is found is in marine bacteria, so the hypothesized source was that gut bacteria used horizontal transfer to acquire the genes from bacteria present in seaweed in the diet. When this possible transfer occurred is unknown and one of the individuals studied was an unweaned infant, so it is possible it has been transferred maternally though many generations.

Gene transfer can only occur from living bacteria. Changes in the modern human diet may reduce the incidence of this happening. Cooking destroys bacteria, but there is an increasing drive towards sterilizing “raw” foods such as produce and nuts for food safety purposes. Most milk on the market is now pasteurized in order to kill bacteria and interestingly there have been studies showing that children who consume raw milk have lower levels of allergies and asthma (Waser et al., 2007) and children growing up in rural environments in general have lower levels of these diseases. Out of such observations the “hygiene hypothesis” was born (Yazdanbakhsh, Kremsner, & van Ree, 2002) which posits that lack of other species in our guts from bacteria to parasites is behind many “diseases of civilization.”

There are several recent developments besides dietary changes that make analyzing the gut bacteria of modern humans to provide evolutionary clues somewhat difficult. Maternal transmission is interrupted in children born by Caesarean section, who do not pass through the birth canal (Grönlund, Lehtonen, Eerola, & Kero, 1999). Antibiotics can also alter gut flora, though to what extent is controversial. Current evidence shows anti-biotic changes, including the presence of bacteria with antibiotic-resistant genes, persisting for over four years (Jernberg, Löfmark, Edlund, & J. Jansson, 2010)
 

Bode, L. (2009). Human milk oligosaccharides: prebiotics and beyond. Nutrition reviews, 67 Suppl 2, S183-91. doi: 10.1111/j.1753-4887.2009.00239.x.
De Filippo, C., Cavalieri, D., Di Paola, M., Ramazzotti, M., Poullet, J. B., Massart, S., et al. (2010). Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proceedings of the National Academy of Sciences, 107(33), 14691-14696. doi: 10.1073/pnas.1005963107.

Gibson, G., Roberfroid, M. B., & Louuain, C. D. (1995). Critical Review Dietary Modulation of the Human Colonie Microbiota : Introducing the Concept of Prebiotics. Journal of Nutrition, (August 1994).

Grönlund, M. M., Lehtonen, O. P., Eerola, E., & Kero, P. (1999). Fecal microflora in healthy infants born by different methods of delivery: permanent changes in intestinal flora after cesarean delivery. Journal of pediatric gastroenterology and nutrition, 28(1), 19-25. Retrieved May 9, 2011, from http://www.ncbi.nlm.nih.gov/pubmed/9890463.

Guarner, F., & Malagelada, J.-R. (2003). Gut flora in health and disease. Lancet, 361(9356), 512-9. doi: 10.1016/S0140-6736(03)12489-0.
Hehemann, J.-H., Correc, G., Barbeyron, T., Helbert, W., Czjzek, M., & Michel, G. (2010). Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota. Nature, 464(7290), 908-12. doi: 10.1038/nature08937.

Henry, A. G., Brooks, A. S., & Piperno, D. R. (2010). Microfossils in calculus demonstrate consumption of plants and cooked foods in Neanderthal diets (Shanidar III, Iraq; Spy I and II, Belgium). Proceedings of the National Academy of Sciences of the United States of America, 1-6. doi: 10.1073/pnas.1016868108.

Jernberg, C., Löfmark, S., Edlund, C., & Jansson, J. (2010). Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology (Reading, England), 156(11), 3216-3223. doi: 10.1099/mic.0.040618-0.

Khoruts, A., Dicksved, J., Jansson, J. K., & Sadowsky, M. J. (2010). Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea. Journal of clinical gastroenterology, 44(5), 354-60. doi: 10.1097/MCG.0b013e3181c87e02.

Leach, J. D., & Sobolik, K. D. (2010). High dietary intake of prebiotic inulin-type fructans in the prehistoric Chihuahuan Desert. British Journal of Nutrition, 103(11), 1558-1561. Retrieved May 10, 2011, from http://journals.cambridge.org/abstract_S0007114510000966.

Ley, R. E., Peterson, D. A., & Gordon, J. I. (2006). Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell, 124(4), 837-48. doi: 10.1016/j.cell.2006.02.017.

McKenna, P., Hoffmann, C., Minkah, N., Aye, P. P., Lackner, A., Liu, Z., et al. (2008). The macaque gut microbiome in health, lentiviral infection, and chronic enterocolitis. PLoS pathogens, 4(2), e20. doi: 10.1371/journal.ppat.0040020.

Tuohy, K. (2003). Using probiotics and prebiotics to improve gut health. Drug Discovery Today, 8(15), 692-700. doi: 10.1016/S1359-6446(03)02746-6.

Urashima, T., Odaka, G., Asakuma, S., Uemura, Y., Goto, K., Senda, A., et al. (2009). Chemical characterization of oligosaccharides in chimpanzee, bonobo, gorilla, orangutan, and siamang milk or colostrum. Glycobiology, 19(5), 499-508. doi: 10.1093/glycob/cwp006.

Waser, M., Michels, K. B., Bieli, C., Flöistrup, H., Pershagen, G., Mutius, E. von, et al. (2007). Inverse association of farm milk consumption with asthma and allergy in rural and suburban populations across Europe. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 37(5), 661-70. doi: 10.1111/j.1365-2222.2006.02640.x.

Yazdanbakhsh, M., Kremsner, P. G., & Ree, R. van. (2002). Allergy, parasites, and the hygiene hypothesis. Science (New York, N.Y.), 296(5567), 490-4. doi: 10.1126/science.296.5567.490.

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For me paleo/evolutionary nutrition is a dietary philosophy rather than a diet. What's the difference? A diet implies following certain rules. And rules really just aren't my thing...

Instead, I prefer to use evolutionary science to think about food, which really does not generate rules, but ideas for us to test out on ourselves while in the pursuit of better health.

It's a little more unsettling: wouldn't it be nice just to have the ability to have a little piece of paper with ten paleo rules to follow? People keep trying to do that, but it doesn't work and it does a great disservice. People follow a rule-based paleo diet and don't do well...and they assume that the paleo diet is a bad one.

Sometimes people see me sprinkling salt on my food and ask "Is that OK on paleo? I thought rule #494494 said no salt?" I would agree that our paleolithic ancestors probably didn't eat added salt and some people have seen huge benefits eliminating it. But rapid genetic change is real, and I seem to carry a gene that predisposes me to hypotension and was a possible cause of the episode that hospitalized me last month (the article mentions how such patients often crave unusual salty foods like pickle juice. My own craving lately is Tibetan butter tea). I feel 100% better on a higher-salt diet.

Another perhaps more common genetic variant causes hemochromatosis, which leads to iron overload. A diet high in red meat would probably be problematic for someone with hemochromatosis, but does that mean they should throw out the idea of following paleo? 

If paleo is about certain foods or certain ratios, yes, but it isn't. An evolutionary paradigm combined with individualized experimentation can lead to many varied diets that fall under the umbrella of paleo. It's perhaps possible in the future that better genetic analysis will help people decide what types of food are best for them, but for now we have to experiment.

Sometimes people will furtively mention potatoes to me, as if it's a possible crime and they have to insert it into the conversation with surgical precision. Probably some Paleo Fascist told them via Twitter that potatoes are the spawn of the neolithic devils and will cause them to explode, especially when topped with a delicious mix of chives, salty bacon, and luscious sour cream.

So when you see someone on teh interwebs telling you that you must do X or you can only eat one type of Y or if you combine X and Y you will turn into a tribble...ignore it. Some people are doing all meat, others high-carb. Some eating no dairy, others eating mostly heavy cream. You can find people thriving on all these variations. It's confusing to see people do really well on a type of diet that would make you overweight and sick, but that's human variation for you.