Monday, December 1, 2014

The History of Gut Bugs--Part 2 of 3

A man and his microbes (or maybe Tail Wagging the Dog?)

Three key features make humans ideal hosts for intestinal microbes[2]:

        An adaptive immune system
        A desire to survive by adapting to external forces
        Lots of food and a stable environment

If microbes had a hand in the evolution of living creatures, their crowning achievement was us.

Microbes have one goal.  Survival.  They will be here long after we are gone, but I'm pretty sure they want to keep us around as long as possible.  Undoubtedly, the lives of gut bugs are much simpler with easily controllable human pods to live in.

The goals of human intestinal microbes and our goals as humans align perfectly.  A human gut bug’s wish list is simple:  A well-fed, long-living, healthy, sociable host who has a strong desire to mate.  The colonization process begins before birth, microbes begin populating places they normally are not seen such as mammary glands, birth canal, and even in the bloodstream.  When a baby is born, the first thing it encounters is a barrage of microbes who want to get inside of the new life form.  They want to become incorporated and create a superorganism.   

Every facet of our lives and behavior is influenced by the lessons our microbes learned in the last 3 billion years[3].  Our social habits, hand-shaking, kissing, hugging, sniffing, licking, and the need for kinship may certainly be all gut-bug driven to access more gut bugs and protect us against pathogens[4].  Often our interpersonal behaviors seem a bit odd, but for our intestinal inhabitants, they may have deep evolutionary meaning.

Gut bugs also hit the jackpot with humans in terms of fueling their existence. Humans are omnivores, meaning we can eat a wide range of foods of plant and animal origin.  Our intestinal microbes need this diversity to keep their living conditions stable.  A diet too high in animal or too high in plant may rock their world[5]!  Back when we were hunters and gatherers, gut microbes might have had an easier time making their human hosts understand their need for different foods.  In the modern day, we are killing them and ourselves with our desire for foods that neither benefit them nor us.   It’s almost a case of the student outsmarting the teacher.


100,000 years ago, we had spread across Africa and into the Middle East.  70,000 years ago we were well established throughout Asia.  50,000 years ago, mankind called most of Europe and Australia home.  At 25,000 years ago, we inhabited the cold regions of Siberia and shortly thereafter, traveled across the Bering Land Bridge into North America.  By 12,000 years ago, we were rooted on nearly every square inch of the Earth’s landmass.

All throughout this amazing journey, our Paleolithic predecessors ate a similar diet...small and large mammals, reptiles, amphibians, fish, birds, grub, insects, plants, tubers, and roots of all kinds.  Everywhere man went, he had access to a vitally important food source: Foods for our intestinal friends. Foods we now consider prebiotics...the fibers, resistant starches and other indigestible bits and pieces of common plant and insect-based foods.  

Prebiotics were extremely important to early man.  Our microbes that keep us healthy and motivated evolved on diets high in fiber and starch[7].  Without this fuel to feed our trillions of microbial friends, we are at a distinct disadvantage in keeping up our end of the deal—the gut bugs’ survival.

Across Africa, Asia, Australia, Europe, and the Americas, prebiotic fiber and starch sources grew plentifully.  They grew above ground and underground. As dry climate swept through after each cold spell, grass-like sedges, prairies and acres of grasslands replaced dense forest.  Besides potatoes and tubers, the new grass-like sedges and grasses provided nutrient rich bulbs, rhizomes and corms. Tiger nuts, sedge bulbs, bananas, plantains, sago, taro, cassava, mung beans, amaranth, squash, cattails, corn, seeds, and nuts were ushered in as the air became more arid and photosynthesis evolved in the dry climes, these are now known as C4 plants[8][9].  When our expansion stopped and man became more dependent on agriculture, our reliance on the plants of our past diminished.

Currently 95% of Earth's plants are the type known as “C3,” however our human food crop plants are nearly all “C4.”  Photosynthesis allows the capture of energy (CO2 and sunlight) to be placed in glucose as chains and polymers or glucose in plants, known as starches and polysaccharides. C4 plants are much more efficient at converting sunlight to compounds humans can use as energy. 

Covered in dirt and soil microbial organisms, sedge bulbs were consumed raw, uncleaned and whole. Dirt and soil based organisms covered these underground storage gems. Early man likely ate it all and on a regular basis. In their soil community, soil organisms consume starches, fiber and as well each other[12]. Encrusted on a starchy tuber, dirt bugs rode into history. Together they represent a synergistic powerhouse of both prebiotics and probiotics.

As progress marched forward into the 21st Century, the consumption of prebiotics is only a fraction of what our ancestors co-evolved with.  Tasty, marketable foods have replaced our old staples, and our gut bugs don’t enjoy it one bit!

Remember earlier, we said that humans made a perfect scaffold for gut bugs to call their native land.  Our propensity to eat a wide range of foods that could not be digested by us made our large intestines a perfect place for microbes to call home. Intestinal microbes rely on a fresh influx of fiber fuel daily for both our survival and their longevity[15].  The modern diet provides food for us, however it’s inadequate for them.This has been the biggest miscalculation by man in our long history despite the wealth of food in modern nations.   

This single faux pas has perhaps lead to widespread disease, early death, and loss of reproductive capacity.  A diet which starves the gut bugs is a diet which dooms mankind.  An agricultural industry which relies on chemical herbicides, pesticides, and fertilizer to grow genetically modified organism (GMO) crops that emit intestinal toxins is an industry which is devastating to the intestinal cities in our guts[16].  Relying on a herd of animals force-fed antibiotics, growth hormones, and fed GMO grains while being raised in a high-stress environment will ensure a meat supply of inferior grade that passes it’s weaknesses to the consumer.  Similarly, a health care industry dependent on antibiotics which indiscriminately kill both good bugs and bad bugs is an industry which delivers unbalance to man.


The trillions of microbes in our gut are credited with influencing the development of the brain, brain chemistry, and a whole range of behavioral systems such as satisfaction, serenity, sadness, pain, and stress.

The small intestine, where we absorb all of our food, has 100 million nerve connections. As the interface with the outside world, it is no wonder that the number of neurons in the gut exceeds that of both the spinal cord and peripheral nervous system combined. Microbes that live there produce hundreds of chemicals, or neurotransmitters, that the brain uses to regulate such things as learning, memory, mood, sleep, and dreaming[19].  The same amount of dopamine, the reward chemical, housed in the gut is the same as the brain's. Nearly all (95%) of our happy mood chemical, serotonin, is manufactured in the gut by a combination of microbial action and intestinal modifications.

This nervous system in our innards is the same one that originally emerged in vertebrates over 500 million years ago. However, as our ancient cranium and brain tissues tripled in size, we believe it is highly likely the 'second brain' and its special inhabitants increased in complexity and magnitude as well[20]. Gastroenterologist Emeran Mayer, MD, director of the Center for Neurobiology of Stress at UCLA once remarked,

“When you consider the gut's multifaceted ability to communicate with the brain, along with its crucial role in defending the body against the perils of the outside world, it's almost unthinkable that the gut is not playing a critical role in mind states[21]."


It may be fanciful thinking that our gut bugs are actually controlling our thoughts and behaviors, but consider if you will for a moment, the amazing life-cycle of the lancet liver fluke (Dicrocoelium dendriticum[22]).  The tiny lancet liver fluke is a parasite that infects mostly cows, although human’s have been known to harbor this pathogen also[23]. It spends its entire adult life inside the host's liver.  After the liver fluke mates, its eggs are excreted in the feces of its host.

The route in which the fluke takes to get from an egg on the ground to an adult living happily in a cow’s liver is nothing short of miraculous.  The first step in completing its life cycle involves being eaten by a snail, feeding on cow dung.  Once eaten, the egg hatches and the larval liver fluke drills into the gut wall of the snail which irritates the snail.  When the snail senses the parasitic intruder it builds a protective cyst around it and excretes it onto the ground.   

Along comes an ant who is following the snail’s trail and using the snail slime as a source of hydration.  The ant finds the cyst, which resembles one of his favorite foods, snail poop, and he eats it.  The liver fluke eats his way out of the cyst and spends a few days drifting around inside the ant’s body fluids until it finds the ant’s “sub-esophageal ganglion,” a cluster of nerve cells similar to a human’s brain, and attaches itself to it.   

The fluke is now in control of the ant.  As evening approaches, the ant, who has behaved normally all day—foraging and feeding with his hill-mates—instead of returning to its colony, the fluke controls the ant and commands it to climb and clamp onto the tip of a very tall blade of grass. In this manner, a grazing cow should come along shortly and eat the grass with the infected ant and thus complete its life cycle.  However, if a cow does not come along before dark, when a nocturnal grazer such as a rabbit or a deer might eat it instead, the liver fluke-controlled ant will unclamp its jaws and return to its anthill as if nothing had happened.  It will repeat the evening grass-climbing act until the ant dies, or a cow eats it.

This bizarre behavior of a single liver fluke inside a single ant seems like a novelty, but similar life cycles are played out by thousands of species of parasites on hundreds of different animals every day[24].  And to then realize that the lowly liver fluke also has microbes living inside it truly makes this story all-the-more bizarre[25].

With these illustrations, the true power of the brain-gut connection should be apparent and the possibility that our gut bugs are more than passive companions becomes a reality.

In humans, toxoplasmosis[26] is caused when the single-celled bacterium Toxoplasma gondii is passed from a cat to a human and infects the human’s brain leading to possible encephalitis (inflammation of the brain) and neurological diseases, and can affect the heart, liver, inner ears, and eyes.  Toxoplasmosis is also associated with attention deficit hyperactivity disorder, obsessive compulsive disorder, schizophrenia, and suicidal behavior.  Toxoplasmosis is also known as ‘Crazy Cat Lady Syndrome[27]’.

Who's really in charge?

[1] "ecology -- Encyclopedia Britannica -" 2008. 1 Feb. 2014 <>
[2] Ley, Ruth E et al. "Worlds within worlds: evolution of the vertebrate gut microbiota." Nature Reviews Microbiology 6.10 (2008): 776-788.
[3] Hickman, Carole S. "How have bacteria contributed to the evolution of multicellular animals?." The Influence of Cooperative Bacteria on Animal Host Biology (2005).
[4] Hendrie, CA. "Kissing as an evolutionary adaptation to protect against Human ..." 2010. <>
[5] Flint, Harry J et al. "Interactions and competition within the microbial community of the human colon: links between diet and health." Environmental microbiology 9.5 (2007): 1101-1111.
[6] "Online NewsHour: Search for Ancestors | Map of Human Migration ..." 2006. 17 Jan. 2014 <>
[7] Ley, Ruth E et al. "Worlds within worlds: evolution of the vertebrate gut microbiota." Nature Reviews Microbiology 6.10 (2008): 776-788.
[8] "C4 plant - definition from" 2006. 1 Feb. 2014 <>
[9] "Staple Crops of the World - Encyclopedia of Life." 2011. 24 Jan. 2014 <>
[10] Lee-Thorp, J. "From the Cover: Isotopic evidence for an early shift to C4 resources ..." 2012. <>
[11] "Grok Didn't Take Supplements So Why Should I? | Mark's Daily Apple." 2008. 5 Feb. 2014 <>
[12] Fierer, N. "Cross-biome metagenomic analyses of soil microbial communities ..." 2012. <>
[13] Montmayeur, JP. "Evolutionary Perspectives on Fat Ingestion and Metabolism in Humans." 2010. <>
[14] Hunter, P. "We are what we eat. The link between diet, evolution and non ..." 2008. <>
[15] "Your Gut Bacteria Are What You Eat | Science/AAAS | News." 2013. 24 Jan. 2014 <>
[16] Dona, A. "Health risks of genetically modified foods." 2009. <>
[17] "Think Twice: How the Gut's "Second Brain" - Scientific American." 2014. 24 Jan. 2014 <>
[18] "Your Backup Brain | Psychology Today." 2011. 24 Jan. 2014 <>
[19] "Gut instincts: The secrets of your second brain - New Scientist." 2012. 6 Feb. 2014 <>
[20] "The Second Brain - HarperCollins Publishers." 2010. 6 Feb. 2014 <>
[21] "That gut feeling - American Psychological Association." 2012. 17 Jan. 2014 <>
[22] "Dicrocoelium dendriticum - Wikipedia, the free encyclopedia." 2006. 24 Jan. 2014 <>
[23] Schweiger, F. "Dicrocoelium dendriticum infection in a patient with Crohn's disease." 2008. <>
[24] "Infection Landscapes: Liver Flukes Part 1: Clonorchis sinensis." 2012. 17 Jan. 2014 <>
[25] Abebe, Eyaulem et al. "An insect pathogenic symbiosis between a Caenorhabditis and Serratia." Virulence 2.2 (2011): 158-161.
[26] "CDC - Toxoplasmosis." 2010. 17 Jan. 2014 <>
[27] Rebecca Skloot. "'Cat Lady' Conundrum, The - New York Times." 2007. 17 Jan. 2014 <>


  1. Toxoplasmosis is weird. An infected rodent will actually charge a cat. Result, dead rodent, infected cat. Coincidence?

    1. Those cats must think they just hit the jackpot!

      Apparently toxo causes mice to lose their fear of the smell of a cat, and people who are infected (which is quite a few from what I understand) also have altered sense of smells. Here's an interesting (nonscientific)article on it:

  2. Fascinating Tim.

    Here is a link to an excellent review on the future of knowledge about the fish microbiome. Fish and their colons and bugs have been around for 600 odd million years and foods are probably not much different over this period. They might have had better chitinase enzymes to generate carbohydrates during earlier times though.!po=2.94118

    1. Dr. j - Nice article! I kept wondering why I was seeing so much about the zebrafish, then I ran across the Zebrafish Genome Project. In 2001, the entire genome of the zebrafish was sequenced and now it is used as a model for other genome sequencing projects. Apparently, you have to do one sequence 'the hard way' and then other people can use your results to more easily sequence similar genomes.

      So, not only have they sequenced the zebrafish' entire genome, they've also sequenced its gut bugs' genome...that's amazing.

      I can't believe how far we've come in the last 10 years with genomes and a better understanding of how everything fits together.

  3. Survive. Eat. Multiply. Spread.

    Now I see the reason you laughed :-)

  4. Hi Tim. Maybe you cover this in part 3 but I'm not seeing the clear causal links in the article which you are trying to make of how gut bugs are benefiting human health and supporting this statement... "A diet which starves the gut bugs is a diet which dooms mankind."

    I'm not criticising and I know the point you are trying to make, but it reads to me a bit like an opinion instead of being clearly explained HOW this hypothesis is supported by the data and WHY it should be believed.

    1. All will soon be revealed! (spoken in a guru-ish accent)

      I think that statement came from cumulative thoughts on the subject. It is my opinion, sure. You will not find that exact statement in a study on PubMed. I think it is 100% accurate, though.

      I think the data shows that our gut bugs do so much for us, and as we get further and further away from eating and living with them in mind (C-sctions, antibiotics, sterilizing everything we touch and eat, etc..) we are creating a race that is unsustainable.

      The recent increase in Lyme disease is not a statement on growing numbers of ticks, it's a statement on the weakened immune systems of people. Same for C-Diff infections, and MRSA infections. And probably Ebola and AIDS.

      You know how dogs can eat rotten carcasses and maybe only puke? It's their gut bugs that protect them from the salmonella and anthrax they also ingested.

      Without a properly functioning gut microbiota, our immune system only is half or less of what it could be.

      I'm not sure if Part 3 will clear all that up, but I probably have some more to post on the subject!


    2. Tim -

      I suppose you've seen this? Pretty cool

      Also, have you seen the movie Wall-E? It seems to me there are some parallels.

    3. No I had not seen that! Cool. A breakdown of a vultures gut flora:

      " Clostridia and Fusobacteria, widely pathogenic to other vertebrates, dominate the vulture’s gut microbiota."

      Haven't seen Wall-E. "Horton Hears a Who" is all I needed to convince me.

    4. Tim, interesting what you said about diseases and specifically Lyme disease. My sister contracted Lyme disease. She has been a vegetarian for decades and more recently added home sourced eggs and goat dairy back into her diet. I wonder how much effect gut bugs and some missing nutrients in her diet (back when she was not eating eggs/dairy) had to do with it.

      Btw, bumped into this about Tortoises, which can live to twice the age of humans, and wondered how many other animals do this...

      "Many tortoises routinely eat their droppings, probably to extract more nutrients or to get the healthy microbes in it."