The History of Gut Bugs--Part 1 of 3

They’re HOW old?

Whether you believe in evolution, or some other theory of how life came to be on this blue planet we call Earth, is irrelevant.  What is important is that you understand the magnitude of our gut microbiome and that, no matter how we got here, the trillions of bacteria in our gut were with us from the very first breath we collectively took as humans. 

We are using the framework here that the Earth is roughly 4 billion years old[1], and humans have been around for a couple million years[2]...if that offends you, well, sorry, but we have to start somewhere!  Single-celled microbes seemingly left their mark in the fossil record 3.5 billion years ago.  As impossible as that sounds, it’s true.  University of Berkeley researchers explain how the process works:

“It may seem surprising that bacteria can leave fossils at all. However, one particular group of bacteria, the cyanobacteria or "blue-green algae," have left a fossil record that extends far back into the Precambrian - the oldest cyanobacteria-like fossils known are nearly 3.5 billion years old, among the oldest fossils currently known. Cyanobacteria are larger than most bacteria, and may secrete a thick cell wall. More importantly, cyanobacteria may form large layered structures, called stromatolites (if more or less dome-shaped) or oncolites (if round). These structures form as a mat of cyanobacteria grows in an aquatic environment, trapping sediment and sometimes secreting calcium carbonate. When sectioned very thinly, fossil stromatolites may be found to contain exquisitely preserved fossil cyanobacteria and algae.” 

Following our single-celled bacterial ancestors’ “reign of terror” that lasted nearly 2 billion years, the first multi-cellular creatures appeared on the scene “just” 1.5 billion years ago. As the days wore on and this early life became increasingly complex, it began taking on odd new shapes as it competed for the food and resources to stay alive. Endosymbiosis is when one microbe lives inside of another to each other's mutual benefit[3]. This is a leading theory on the origins of specialized cells and multicellular life[4]. So, not only does it seem that microbes want inside of every living thing, they also want inside each other.

Endosymbiosis run amok!

Inside of a common mealybug, Planococcus citri, lives a bacterium known as Tremblaya princeps, who has its own resident microbes—Moranella endobia[5].

None of these three inter-nested species can live on its own, they are completely dependent on each other, however, the pesky mealybug is no slouch!  During mating, the citrus mealybug is known to engage in "triple coitus"; a female may copulate with two males at the same time, and a third male may at least make attempts to join the process. Males spend the one or two days of their adult lives mating, and have been observed achieving copulation with up to 23 females, with an average of about nine[6].

We often ask, “which came first, the chicken or the egg?” but in the case of microbes and animals, the answer is easy—microbes!  The fact that not only were microbes the first life on earth, but also likely colonized the earliest life forms, explains perhaps why they exert such dramatic control on their hosts[7].  It should give us pause that we ignore the symbiotic relationship that microbes create in regards to our brain function, metabolism, immunity, structure and function of the digestive system (their humble home).

Fast-forward to the scene where the human comes in...

Two things are central to man’s evolution:  Intestinal microbes and food[8].  Man evolved in two distinct phases; the first half, where we split from apes, lasted for about 2 million years.  During this timeframe, human lines began to eat more seeds, soft fruits, and foraged for small animals.  The second phase of man’s evolution was shaped by vast climate changes as the Ice Ages shifted Earth’s climate to cool, dry, and more variable, lasting about another million years.  Towards the end of this half, grasses, grains, legumes, and tubers thrived wildly and replaced the lush leaves and fruit-bearing forests.

Among the changes in food sources for our ancestors, three distinct dietary patterns emerge in the historical story. These are vital to understand because as nutritional sustenance rapidly changed, so did selection for adaptations in the gut. The weather driven changes of the last half of our evolutionary transition critically shaped both humans and the microbes inhabiting their digestive systems by affecting how we found food and what food we put into our mouths.

One theory, known as the ‘grandmother hypothesis’, speculates that older females did most of the foraging for early societies[9].  This may have thrust  ‘underground storage organs’, that is, plant roots, bulbs, and tubers, into a reliable avenue of nutrient dense food[10].  The grandmother hypothesis was derived by watching the Hadza people in Tanzania, the older women of this group of traditional foragers were observed to forage for tubers and care for children. This ‘grandmotherly’ support of grandchildren ensures their daughters may bear more prodigy as they are freed of some of the childcare duties particularly whilst pregnant or breastfeeding.  This behavior is unique among animals.  Although menopause marks the end of a human’s childbearing years, it is not the end of life.  In fact, menopause is a protective mechanism for longevity.  Human beings are the only species with such a long span of life after reproduction. For most animals, the basic function for the female is to reproduce.  In most species, after reproductive capacity is lost, the females will soon die.  Postmenopausal longevity is a trait that is exclusively human.

Perhaps the cooperative caregiving and foraging of soil-encrusted, luxurious underground tubers to feed toddlers and mothers by grandmothers bankrolled the massive gains in human brain size.  That is what some academics think[11].  As human babies were born with more helplessness and prematurity and requiring more care, the human brain doubled in size the during this last half of our evolution[12].

The ‘Expensive Tissue Hypothesis[13]’ describes a second major diet shift in human evolution.  During the Pleistocene era, approximately 2 million years ago, Homo began eating more meat.  This move may have been critical for the development of a larger brain.  By the Paleolithic era, 1 million years ago, stone-tool manufacturing became commonplace.  With Homo Neanderthalensis from 30,000 to 400,000 years ago, big-game hunting monumentally characterized one line of our ancestral forefathers.

A third major change in diet came about 10,000 years ago with the adoption of agricultural practices and the domestication of animals, particularly dairy animals.  This method of food procurement replaced hunting and gathering and by the early 1600s had affected nearly every person on Earth.

Each one of these changes in human diet left indelible marks in our DNA and that of our gut bugs.  One of the most important changes was reflected in our ability to digest starch. Humans possess a specific gene which allows for starch breakdown, known as salivary amylase, or “AMY1”[14], humans possess this gene at roughly three times the rate of our nearest primate relatives.  Additionally, ancestors of people who traditionally ate high starch diets have more copies of this gene than ancestors of people who ate relatively little starch.  Was this desire to seek out and eat starchy foods our idea—or our gut bugs’?  You decide.

From a 2007 study[15] on the number of genes we have to digest starch:

“In summary, we have shown that the pattern of variation in copy number of the human AMY1 gene is consistent with a history of diet-related selection pressures, demonstrating the importance of starchy foods in human evolution. While the amylase locus is one of the most variable in the human genome with regard to copy number, it is by no means unique; a recent genome-wide survey identified 1,447 copy number variable regions among 270 phenotypically normal human individuals, and many more such regions will likely be discovered with advances in copy number variation detection technology.”

And what were the gut bugs doing this whole time?

In the very early years of microbe evolution, before there were animal hosts, microbes began splitting into two groups—those that could survive in salt-water, and those that could survive in the absence of salt-water[16].  When the first animals arrived on the scene, these free-living microbes were integrated into their lives and split into groups based on the diets of their new hosts.[17]

As different lines of animals began to appear from fish to amphibians to reptiles, birds, and mammals, different lines of gut bugs also appeared along with each new animal type.  As many of the mammals split into carnivores, herbivores, and omnivores, distinctions in gut bugs became apparent.  It is interesting to note that the gut bugs of meat-eating carnivores more closely resemble saltwater, free-living species of microbes than the gut bugs of plant-eaters. 

The pattern is as clear today as it was millions of  years ago: mammals with similar diets and patterns harbor similar microbes.[18]

Single-celled microbes are no dummies!  They survived over a billion years on their own, then another billion years alongside the simplest of life.  When advanced life forms began to appear, these microbes saw an opportunity to advance and survive, so they seized a host and became forever intimately tied with animal life.  Together with their host, they are known as ‘Superorganisms’[19], an organized society that functions as a whole.

Other notable superorganisms[20]:

- Ants

- Bees, wasps

- Termites

- Naked Mole Rats

A superorganism is a collection of living things which rely on each other for their existence.  Individuals of the superorganism cannot survive long on their own outside the collective.  First thought to apply only to insects like ants, bees, and termites, other superorganisms have been identified that are not insect in nature.  The Naked Mole Rat of eastern Africa is one such superorganism. 

Naked Mole Rats feel no pain, literally, they have no pain receptors in their brain.  They also have no ability to regulate their body temperature and must huddle together to survive, they are the only cold-blooded mammal in existence.  Each Naked Mole Rat colony consists of one breeding female (the Queen) and three breeding males...all of the rest of the Naked Mole Rats in a colony are sterile and destined for tunnel building, food collection or maintaining the safety of the nest. When a queen dies, a battle royale between the colony’s females ensues and the victor becomes the new queen.  The new  Naked Mole Rat queen then undergoes a seemingly impossible and completely unique physical transformation, stretching the spaces between her vertebrae, becoming longer, and activating her once-sterile reproductive organs to bear young.

The queen bears several litter of young each year.  They are born blind and nursed for 30 days, after that, they are fed feces for several weeks until they are old enough to eat solid food. 

These Naked Mole Rat colonies, often consisting of up to 300 individuals, center their lives around large underground tubers which can feed the colony for several years.  The Naked Mole Rats have virtually no digestive enzymes and rely completely on their intestinal microbes to digest the indigestible fibers of the tuber. 

Despite these seemingly deleterious conditions, naked mole rats live to be 30 years old in the wild (the longest among rodents) and never get cancer[21].  What do you want to bet gut bugs play a role?         

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^[1] "Evolution: Frequently Asked Questions - PBS." 2002. 17 Jan. 2014 <http://www.pbs.org/wgbh/evolution/library/faq/cat06.html>

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^[3] "Why Metagenomics? - The New Science of Metagenomics - NCBI ..." 2011. 24 Jan. 2014 <http://www.ncbi.nlm.nih.gov/books/NBK54011/>

^[4] "The Evolution of the Cell - Genetic Science Learning Center." 2014. 17 Jan. 2014 <http://learn.genetics.utah.edu/content/cells/organelles/>

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^[6] "Planococcus citri - Wikipedia, the free encyclopedia." 2006. 17 Jan. 2014 <http://en.wikipedia.org/wiki/Planococcus_citri>

^[7] "Microbes can influence evolution of their hosts - Science Daily." 2013. 17 Jan. 2014 <http://www.sciencedaily.com/releases/2013/07/130718142417.htm>

^[8] "Introduction to Human Evolution - Human Origins Program." 2010. 17 Jan. 2014 <http://humanorigins.si.edu/resources/intro-human-evolution>

^[9] Marlowe, F. "THE PATRIARCH HYPOTHESIS - Harvard University." 2000. <http://www.fas.harvard.edu/~hbe-lab/acrobatfiles/patriarch.pdf>

^[10] Hernandez-Aguilar, RA. "Savanna chimpanzees use tools to harvest the underground storage ..." 2007. <http://www.ncbi.nlm.nih.gov/pubmed/18032604>

^[11] Hawkes, Kristen et al. "Grandmothering, menopause, and the evolution of human life histories." Proceedings of the National Academy of Sciences 95.3 (1998): 1336-1339.

^[12] Isler, Karin, and Carel P van Schaik. "Allomaternal care, life history and brain size evolution in mammals." Journal of human evolution 63.1 (2012): 52-63.

^[13] Aiello, Leslie C, and Peter Wheeler. "The expensive-tissue hypothesis: the brain and the digestive system in human and primate evolution." Current anthropology 36.2 (1995): 199-221.

^[14] "Amylase." 2011. 24 Jan. 2014 <http://www.princeton.edu/~achaney/tmve/wiki100k/docs/Amylase.html>

^[15] Perry, George H et al. "Diet and the evolution of human amylase gene copy number variation." Nature genetics 39.10 (2007): 1256-1260.

^[16] "Evolution 101: From Soup to Cells - the Origin of Life." 2004. 17 Jan. 2014 <http://evolution.berkeley.edu/evosite/evo101/IIE2aOriginoflife.shtml>

^[17] Ley, RE. "PMC free article - National Center for Biotechnology Information." 2008. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2664199/>

^[18] Ley, Ruth E et al. "Worlds within worlds: evolution of the vertebrate gut microbiota." Nature Reviews Microbiology 6.10 (2008): 776-788.

^[19] Sleator, RD. "The human superorganism - of microbes and men." 2010. <http://www.ncbi.nlm.nih.gov/pubmed/19836146>

^[20] "What is a superorganism? - Curiosity." 2010. 9 Jan. 2014 <http://curiosity.discovery.com/question/what-is-a-superorganism>

^[21] "Naked mole rat may hold the secret to long life -- ScienceDaily." 2012. 3 Feb. 2014 <http://www.sciencedaily.com/releases/2012/07/120702162327.htm>