Please Pass the Microbes
A few days ago I accompanied two Hadza hunters to a series of seeps or springs where they had set up hunting blinds of tall grass to ambush thirsty animals. It’s late dry season in Tanzania and dwindling water sources force otherwise dispersed animals to aggregate, and if you’re a hunter-gatherer, this is a good thing. The week before a hunter killed a zebra from one of these blinds with a poison tipped arrow (a windfall of >400-500 pounds of protein and fat that would be consumed in <72 hours!). On our way back to camp, we came across another Hadza that had moments before killed an adult Impala. After helping hoist the deceased into a low hanging tree – to hang by its head for field dressing – I then witnessed something that up until that point I had not fully appreciated the significance of in the co-evolution of humans and our microbes and its potentially profound implications for our health in the so-called modern world.
I had come to Tanzania as part of a collaboration of US, Canadian, and Tanzanian researchers to try and understand what the gut microbiome might look like in a group that still hunts and forage’s 95-100% of its food and more interestingly, how pronounced seasonal changes in resources – between wet and dry seasons – might impact compositional and functional changes in the microbiota. One pressing question in microbiome research – at least what the public and many public health officials wants to know (not to mention food manufacturers and Big Pharma) – is there an optimal composition of gut microbes we should strive for, and at what age, and what diet and lifestyle choices will get us to this microbial fountain of health. Which is, of course, a complex question.
The Hadza may provide some interesting insight into this question as they live in a part of Africa that presumably gave rise to our genus (Homo) and our more distant tree-hugging ancestors. The Hadza still hunt and forage many of the animals and plants that our ancestors relied upon, are covered in the same soil, drink the same water, and follow more or less a seasonal hunter-gatherer lifestyle that dominated the last two million plus years of human evolution. While its important to understand how humans lived once they left Africa and settled other parts of the planet in the last ~60,000 years, the huge spans of time our kind spent in Africa evolving towards the lion’s share of our current physiology (and current adaptive immunity), is potentially more interesting when it comes to understanding the human-microbe relationship – both good and bad.
Importantly, the Hadza don’t keep livestock or plant foods of any kind, and have limited access to modern medications like antibiotics (at least the more remote Hadza camps that we are studying). While some may argue that the Hadza are not perfect referents for the way it once was, it depends on the questions you are asking. For our purposes, studying how humans acquire microbes from birth throughout life (from others and the larger meta community of microbes in nature) in a group where babies are all still born naturally (no c-sections), are breastfed on average for 2+ years, where children still sleep with their mothers years beyond weaning, take no antibiotics, don’t drink water that has been treated with chlorine and fluoride, where multiple generations stay together (not separating the seniors into assisted living facilities), don’t eat processed foods, and newborns to the eldest in the community are still covered in nature’s blanket of everything that comes from living outside 24/7 and interacting in an intimate way with 100s of species of plants and animals.
Back to the Impala.
Before the two Hadza men I was with jumped in to help skin and gut the Impala, I quickly took swabs of each of their hands (and 1 hour after, 3 hours after, and so on) to assess how the skin (palm) microbiota change throughout the day/week of a typical Hadza (We’ve sampled the hands [and stools] of 150+ Hadza men, women, and children so far). As they slowly and methodically dismembered the animal, they carefully placed the stomach and its still steaming contents on the fleshy side of the recently removed hide. In a separate area, they piled the fatty internal organs (which men are only allowed to eat by the way). Once the animal had been processed more or less, I was amazed to see all three men take a handful of the partially digested plant material from the recently removed stomach to scrub off the copious amounts of blood that now covered their hands and foreman’s. This was followed by a final “cleaning” with dry grass for good measure.
Hadza hand sanitizer – stomach contents from Impala.
While I was fascinated by the microbe-laden stomach contents being used as hand scrubber – presumably transferring an extraordinary diversity of microbes from the Impala gut to the hands of the Hadza – I was not prepared for what they did next. Once they had cleaned out – by hand – the contents of the stomach (“cleaned” is a generous word), they carved pieces of the stomach into bite-sized chunks and consumed it sushi-style. By which I mean they didn’t cook it or attempt to kill or eliminate the microbes from the gut of the Impala in anyway. And if this unprecedented transfer of microbes from the skin, blood, and stomach of another mammal wasn’t enough, they then turned their attention to the colon of the Impala.
After removing the poo pellets (which we collect samples of as well), they tossed the tubular colon onto a hastily built fire. However, it only sat on the fire for a minute at best and clearly not long enough to terminate the menagerie of invisible microbes clinging to the inside wall of the colon. They proceeded to cut the colon into chunks and to eat more or less raw. For myself, I kindly turned down offers to taste either the raw stomach or the partially cooked colon – but did eat some tasty Impala ribs I thoroughly turned on a stick over the fire to a microbial-free state of well done.
The Hadza explained that this is what they always do, and have always done (though I suspect sushi-style eating of innards is not an every-kill ritual. But….). Whether it’s an Impala, Dik Dik, Zebra, bush pig, Kudu or any other of the myriad of mammals they hunt and eat, becoming one with the deceased’s microbes in any number of ways is common place – same goes for 700 plus species of birds they hunt (minus abundant amounts of stomach contents for hand sanitizer!). While less obvious than at the “kill site,” the transfer of microbes continued back in camp when women, children and other men handled the newly arrived raw meat, internal organs, and skin. The transfer continued as the hunters engaged (touching) other members of the camp.
The breathtaking exchange (horizontal transfer) of microbes between the Hadza and their environment is more or less how it’s been for eons until humans started walling ourselves off from the microbial world through the many facets of globalization. Rather than think of ourselves as isolated islands of microbes, the Hadza teach us that we are better thought of as an archipelago of islands, once seamlessly connected to one another and to a larger metacommunity of microbes via a microbial super highway that runs through the gut and skin/feathers of every animal and water source on the landscape (for those of you keeping up with your homework, this is Macroecology 101). The same can be said for plants and their extraordinary diversity of microbes above (phyllosphere) and below ground (rhizosphere) that the Hadza, and once all humans, interacted with on a nearly continuous basis.
The Hygiene Hypothesis – or Old Friends Hypothesis, if you prefer – posits that a great many diseases (specifically autoimmune diseases) result from a disconnect with the natural world and its myriad of microscopic life. Microbes and other tiny things that once trained our immune system to distinguish between friend or foe and even Self. Our children are no longer born in the microbe-rich dirt, but rather hyper-sterile rooms where even the air is scrubbed with mechanical systems. Further, an increasing number of our kids are born through an incision rather than the microbial-rich birth canal and the percentage that are still consuming microbial-rich milk from mom at 2 or even 1 year of age can be counted in the low single digits depending on where you live and your lot in life. Our kids – most of them, or adults for that matter – have no interaction with extensive microbial networks that the Hadza and our ancestors once experienced. For us, the microbial super highway that once connected all humans to the larger metacommunity of microbes now dead ends at closed windows in a home at the end of the street with very few species of plants in the yard and no or few animals – save a dog or two – and a wet wipe and anti microbial something or other at every turn.
All samples are frozen in the field in liquid nitrogen.
There is no arguing that our modern lifestyle and wonders of modern hygiene, sanitation, and medicine have saved a great many lives over previous generations – especially among the youngest in our ranks who are especially vulnerable to diarrheal and respiratory disease (which is still a problem in densely crowded conditions in many developing countries). But as we tout the triumph of modern life span over the more cruel life of the days of yore, we need to keep in mind that our point of reference is the filth and pestilence of the crowded towns and cities of the last millennia or so – not the nomadic lifestyle that dominated 99% of human/hominin evolution before we plowed the ground and pinned select animals. Yes, ~20% of Hadza children die young, but those that survive to adulthood have a good chance to live into their 60s, 70s, and 80s. To suggest that we can’t learn about the very foundations of human-microbe mutualism, commensalism, vertical/horizontal transmission, and microbial succession across an age gradient in a society unencumbered by the confounders of so-called modern life because of childhood mortality rates seen as extreme by modern medical standards, is to throw the baby out with the bath water. The Hadza, and the very limited number of groups like them, are disappearing fast – and this potential microbial Noah’s Ark will soon be lost.
What we might learn from the Hadza’s intimate participation in the microbial super highway of the natural world is made more interesting when you consider a series of experiments recently published in the prestigious journal Science. In an elegant set of experiments, the researchers took poo samples from several sets of twins discordant for obesity and inserted them into germ free mice. In other words, one of the twins was lean while the other a little chunky. As with previous experiments, the transplanting poo from obese twin made the recipient mice obese and the poo from the lean twin resulted in lean mice – demonstrating that host phenotype (obese or lean) is transmissible. I admittedly just glossed over a very detailed study with lots of interesting moving parts – if you have access to this journal, I would highly recommend reading the entire paper. That said, one aspect of the study is worth drawing additional attention – and also happens to be the part of the multi-faceted study that received the most attention from the media.
After taking germ free mice and inoculating them with either the microbiota from the lean or chunky twin – and thus making the bugged mice fat or lean – they then stuck the lean and fat mice together in the same cage and fed them the same diet. Since mice are coprophagic – ie, they eat poo – the researchers were curious to see what happened. Throughout the cohousing of lean and obese mice, the researchers collected fecal samples (careful to keep separate which pellets came from which mouse) every day more or less for a few weeks. They also monitored body composition as well.
Remarkably, analysis of fresh poo pellets from the mice revealed that several species of bacteria from the lean mice successfully invaded the gut of the fat mice, but not the other way around (remember, the mice were eating each others poo and thus each others microbes). In other words, the gut microbiota of the fat mice reconfigured to look more similar to the lean mice – yet, as mentioned, the lean mice microbiota remained stable and did not uptake any bacteria from the obese mice despite eating the fat mice poo. Furthermore, the invasion of species from the lean mice into the obese mice essentially shut down further weight gain in the obese mice. Interestingly, the diet was low fat, high plant polysaccharide and fed ad libitum (all you can eat).
Using a snazzy piece of analytical wizardry, the researchers were able track exactly which species successfully invaded the gut of the obese mice from eating the poo of the lean mice. Of the handful of species that invaded the gut of the obese mice from the lean cage mates, Bacteroides spp. from the phylum Bacteroidetes were largely responsible in protecting against increased adiposity in the fat mice.
Since it appeared that various Bacteroides spp. were not only successful invaders but also conferred some kind of leanness, the researchers cooked up a cocktail of a number of Bacteroides spp. and a handful of others (39 species in all) and did the experiment all over again. This time, they put obese mice in a cage – made obese from the chunky twins microbiota – and cohoused them with originally germ free mice that received only the cocktail of 39 species. This time around, the lean mice poo of the 39 specific species was unable to protect the obese mice from getting chunkier. This experiment demonstrated that its not one strain or handful of strains that confer less adiposity and more leanness in obese mice, but more complex interactions underlie the protection against adiposity.
In one final experiment, they put mice inoculated with the full microbiota from a lean or obese human twin and stuck them in the same cage – same as before. However, this time they changed the diet to high saturated fat, low fruit and vegetable – that is, low fiber. Like the previous experiment, the mice consumed one another’s poo but this time around, bacteria from the lean mice didn’t successfully invade the gut of the obese mice. This suggest the underlying mechanism for protection from obesity in this particular experiment is more complex, possibly involving a great many more community members then just a handful of species and diet dependent.
In the context of the experiments discussed in the Science paper, I can’t help but think that us “moderns” moving through our squeaky clean lives – obsessing over every bite of food we eat – might be suffering oh so slightly from a detour or full blown exit from the microbial super highway that once dominated so much of our evolutionary history. Though the Hadza and presumably our ancestors didn’t directly consume each other feces or that of the animals on the landscape in a deliberate way on a frequent basis, clearly our hunter-gatherer ancestors had a more intimate involvement in the total microbial metacommunity of the environments they inhabited than we do in the concrete jungles we call home.
It’s tantalizing to think that as part of this microbial web, that our ancestors didn’t benefit in some way with the nearly daily sampling and exchange of microbes with animals as diverse as zebra, impala, birds, or even carnivores like lions (which the Hadza eat by the way), or from a dizzying number of plants sprouting from soil teeming with bacteria (and their genes) worth sampling and possibly utilizing for our mutual benefit. Not only is this plausible, it’s highly likely.
**A tiny, tiny version of this blog post appeared in Nature.