Researchers track the gut-brain connection
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People may advise you to listen to your gut instincts: now research suggests that your gut may have more impact on your thoughts than you ever realized. Scientists from the Karolinska Institute in Sweden and the Genome Institute of Singapore led by Sven Pettersson recently reported in the Proceedings of the National Academy of Sciences that normal gut flora, the bacteria that inhabit our intestines, have a significant impact on brain development and subsequent adult behavior.
We human beings may think of ourselves as a highly evolved species of conscious individuals, but we are all far less human than most of us appreciate. Scientists have long recognized that the bacterial cells inhabiting our skin and gut outnumber human cells by ten-to-one. Indeed, Princeton University scientist Bonnie Bassler compared the approximately 30,000 human genes found in the average human to the more than 3 million bacterial genes inhabiting us, concluding that we are at most one percent human. We are only beginning to understand the sort of impact our bacterial passengers have on our daily lives.
Moreover, these bacteria have been implicated in the development of neurological and behavioral disorders. For example, gut bacteria may have an influence on the body’s use of vitamin B6, which in turn has profound effects on the health of nerve and muscle cells. They modulate immune tolerance and, because of this, they may have an influence on autoimmune diseases, such as multiple sclerosis. They have been shown to influence anxiety-related behavior, although there is controversy regarding whether gut bacteria exacerbate or ameliorate stress related anxiety responses. In autism and other pervasive developmental disorders, there are reports that the specific bacterial species present in the gut are altered and that gastrointestinal problems exacerbate behavioral symptoms. A newly developed biochemical test for autism is based, in part, upon the end products of bacterial metabolism.
But this new study is the first to extensively evaluate the influence of gut bacteria on the biochemistry and development of the brain. The scientists raised mice lacking normal gut microflora, then compared their behavior, brain chemistry and brain development to mice having normal gut bacteria. The microbe-free animals were more active and, in specific behavioral tests, were less anxious than microbe-colonized mice. In one test of anxiety, animals were given the choice of staying in the relative safety of a dark box, or of venturing into a lighted box. Bacteria-free animals spent significantly more time in the light box than their bacterially colonized littermates. Similarly, in another test of anxiety, animals were given the choice of venturing out on an elevated and unprotected bar to explore their environment, or remain in the relative safety of a similar bar protected by enclosing walls. Once again, the microbe-free animals proved themselves bolder than their colonized kin.
Pettersson’s team next asked whether the influence of gut microbes on the brain was reversible and, since the gut is colonized by microbes soon after birth, whether there was evidence that gut microbes influenced the development of the brain. They found that colonizing an adult germ-free animal with normal gut bacteria had no effect on their behavior. However, if germ free animals were colonized early in life, these effects could be reversed. This suggests that there is a critical period in the development of the brain when the bacteria are influential.
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23 Comments
Add CommentHow much of what is explained as "inheritable" epigenetics is really due to bacteria? Or perhaps a better way of phrasing it- how much of epigenetics is controlled by bacteria?
Reply | Report Abuse | Link to thisBare with me- I'm not an expert in any of these fields and am just recalling faint memories of odd stories I've read on here or similar sites.
I remember reading one example where people whose ancestors survived famine were more prone to obesity (can't remember why it was stated this was due to epigenetics rather than genetics).
Another study was done with mice and fur colour - I don't remember the details- but a certain stress caused a fur colour change that was passed on to future generations.
Could some- or most, maybe even all epigenetics be explained by bacteria influencing our expression of genes?
If certain populations of bacteria in our body were to die off allowing others that influence us in other ways to bloom; the death or birth of bacteria occupying a specific niche could alter how an organism develops.
I should add- and it is likely that this could/would be inheritable due to the offspring be raised in the proximity to the parents- I presume the original source of our bodies bacteria.
Reply | Report Abuse | Link to thisOoops... sorry one last post and then I'll stop talking to myself.
Reply | Report Abuse | Link to thisHere's a link to inheritable epigenetics in mice:
http://news.sciencemag.org/sciencenow/2006/04/12-02.html
The fact that it seems to be inherited more from the mother would also give credence to the possibility that bacteria perhpas received in the womb or shortly after- could drive the change.
The article states:
Reply | Report Abuse | Link to this"Princeton University scientist Bonnie Bassler compared the approximately 30,000 human genes found in the average human to the more than 3 million bacterial genes inhabiting us, concluding that we are at most one percent human."
This comparison is extremely misleading. The 3 million bacterial genes represent a diverse colony of cells living primarily within the gut. What genes primarily control the production of most human cells outside the gut and their metabolic processes? That bacteria free organisms can function indicates it is the host's genes.
This is not to say that the secondary influences that bacteria may exert over the operatonal conditions of the brain cannot produce significant changes. I have experienced serious degredation of intellectual abilities following extensive chemo regimens that produced severe anemia. That intellectual degredation was only discovered when unrelated prescription of Lovaza (omega-3) very suddenly restored prior capabilities. It is speculated that omega-e intake can restore damaged myelin sheaths electically insulating neruronal axons, improving electrical transmissions between neurons. While this occurrence had nothing to do with genes, it illustrates to me that environmental conditions can produce dramatic changes in brain processing capabilities.
The availability of specific neurotransmitters and their precursors, especially during the critical developmental period of brain plasticity, clearly demonstrated by enhanced language acquisition capabilities, could profoundly affect specific characteristic development of brain capabilities.
I also have to wonder about the potentially more direct effects of any viral cells that might be found operating within the blood-brain barrier.
Very interesting - makes one wonder about the development of the mitochondria within human cells. Could they have originally been separate bacterial cells?
Reply | Report Abuse | Link to this@David N'Gog
Reply | Report Abuse | Link to thisI believe the example you are thinking of in humans was attributed to epigenetics because the study found that the obese individuals had a higher incidence of methylated DNA at the promoter of a gene involved in metabolism - resulting in that gene (or genes) being turned off. This is a classic example of an epigentic effect, the sequence of the DNA remains the same; however, modification of the DNA (or of the histone proteins that package DNA)changes the expression level of a gene. Given the accumulation of data that suggest that the normal gut flora have vastly under-appreciated effects on several aspects of human development and behavior, it would be interesting to see if any of theses effects are mediated through epigentic mechanisms.
There is an abundance of evidence that the mitochondrion evolved from a bacterium, which has lead to the development of 'the endosymbiotic theory.' Similarly, chloroplasts in plants likely evolved from a photosynthetic cyanobacterium.
Reply | Report Abuse | Link to thisWhat if the bacteria in our gut are not "passengers" in humans. What if humans are the most evolved form of life support yet developed by evolution for bacteria?
Reply | Report Abuse | Link to thisI have to say that this article is rather misleading. The embryonic brain development is a multi-step process (I won't go into details here), and while the gut flora can begin a cascade, I highly doubt it has a direct control/influence over the brain development. That is almost like saying that a cut will cause the blood to clot.
Reply | Report Abuse | Link to thisThe mitochondria are thought as once-parasitic part of the cells, but that does not mean that the mitochondria exerts much influence over the mitotic process. After reading this, a layperson may even expect that a human with less bacterial flora within the gut are more brave, or more intelligent. If neurologists/neuroscientists could map out personalities with hormonal balances, we can kiss goodbye to the shrinks.
Much more evidence/research is needed before we reach to conclusions.
I wonder if this provides an explanation for the metabolic differences between people who are skinny and those who are obese.
Reply | Report Abuse | Link to thisThere may be an interplay between metabolism regulation enzymes released by the bones (could the release of these enzymes be regulated by symbiotic bacterial flora?), the bacterial flora in the gut (possibly) influencing the brain's glucose or protein satiation behavior, the methylated DNA or protein package of the genes that makes famine survivors' descendants prone to obesity.
Perhaps as cmelby has pointed out, our bodies are the most evolved package to protect and nourish bacterial flora, and these flora have influenced the evolution of human beings towards obesity, to enhance their own food supply?
Human beings are highly mobile, and our intelligence has allowed our species to conquer virtually every ecosystem on Earth, spreading us into almost every continent, and also multiplying our numbers. The bacterial flora in our gut benefit because they don't have to expend energy to move themselves into new habitats, or enhance existing habitats with ample food supplies.
I had another thought, this is inspired by the body's response to extend its survival during the body's exposure to cold conditions.
Reply | Report Abuse | Link to thisDuring potential exposure to hypothermic conditions, the body will shunt blood flow away from the extremities, to maintain core temperature in the cardio-thoracic region, the abdomen and the brain. This response may be mediated by the gut bacterial flora, to protect itself, and the bare minimum body systems of their host human being to ensure the human being can still seek food and be able to digest it.
The presence of significant amounts of bacterial flora in faeces, is the way gut flora reproduces and spreads into other environmental domains. It is the nature of Life to seek new domains, to multiply, break out from its bounds, and spread into new territory.
jtdwyer's remark about the influence of viruses in the blood-brain barrier is another interesting point.
Reply | Report Abuse | Link to thisI recall reading in Scientific American several years ago, that geneticists found copies of viral DNA incorporated into human genes. There may also be discoveries to be made in studying our bodies' interactions with various viral species.
Perhaps the viruses and some bacterial species, affect human behavior by trying to stop a person's natural tendency to put their hand over their nose or mouth when they cough or sneeze, to promote the spread of viruses and bacteria into the general population?
I also agree with GabrielleD's remarks about the need for much more work to be done in this area before we reach any conclusions. This is why I posed my ideas with words like may, perhaps, or terminate my remarks with question marks. It is still too early to draw any conclusions.
Reply | Report Abuse | Link to thisFor example, the human species has invented mathematics, science, and apply these discoveries through engineering. There is no clear discernible reason how bacteria or viruses can benefit from esoteric pure mathematics; there is no direct survival benefit. The only reason why human beings have developed such advanced technology, is essentially to devise a better and bigger stick to beat up or kill the guys who wear a different uniform, or have a different economic or political ideology.
From the perspective of bacteria or viruses, human wars may be a massive waste of potential habitats for them to seek to spread into/colonise/infect?
I was born with Thrush ,must have gottn it from my mother(1952). I have battled depression since I hit puberty. Wow....maybe thats the reason.
Reply | Report Abuse | Link to thisAh, yes, but the same germ-free mice that exhibited less anxiety also developed motor dysfunction and memory and learning problems (in fact, the lack of anxiety is probably due to short-term memory loss. See http://scienceblogs.com/neurophilosophy/2011/03/gut_bacteria_may_influence_thoughts_and_behaviour.php). I'm wondering if some neurological diseases such as Alzheimer's and Parkinson's are caused by disruption of gut microbia later in life. If so, that might be good news, as disruption later in life may be reversible. (http://www.theamazingagingmind.com/2011/does-alzheimers-take-guts-niacinamide-experiment-part-2/)
Reply | Report Abuse | Link to thisCould be, Marylou. Thrush is caused by Candida which is a prominent yeast in the gut as well. I suspect something similar causing Alzheimer's and Parkinson's.
Reply | Report Abuse | Link to thisthis is interesting timing. the times just put out this article(http://www.nytimes.com/2011/04/21/science/21gut.html?_r=1 ) about a group of german scientists led by Peer Bork that have concluded that people fall into one of three distinct ecosystems in the gut called enterotypes. it is being likened in importance to the value of knowing one's blood type. in light of having just read the times article, i was having a hard time understanding what Petterson's research meant by "normal gut bacteria."
Reply | Report Abuse | Link to thisGiven the several ways bacterial flora can enter our gut and take up residence, might this article be another expression of the adage "you are what you eat (and breathe)?
Reply | Report Abuse | Link to thisI don't know the context of the comment, but it seems pretty clear that it was meant to be tongue-in-cheek. I doubt very much that it was ever meant to imply that humans are 99% non-human.
Reply | Report Abuse | Link to thisthis presents an interesting topic tho, in the last century industrialized countries( mostly the US) have started seeing higher trends of obesity, nuerological disorders, diabetes, allergies, depression, ect. Maybe this could be attributed the the rise and overuse of one thing: antibacterial products. we sterilize everthing a kid uses, and maybe we prevent many children from getting beneficial bacteria critical to development. as this study shows the bacteria does not affect things when presented at older age.
Reply | Report Abuse | Link to thisThere are a number of mechanisms that bacteria use to exert a profound effect on human metabolism.
Reply | Report Abuse | Link to thisThe ENDOTOXINS contained in bacteria, and the EXOTOXINS and ENTEROTOXINS that bacteria continually secrete, all have a profound influence of human metabolism and brain function, as do the ENZYMES bacteria release to alter our biochemistry in their favor.
Any given bacterium may posses a dozen or so different toxins and human metabolism-modulating enzymes which is deploys.
For example, Staphylococcus aureus, found in around the guts of 7% of the population, releases alpha toxin, a potent PORE FORMING TOXIN (which punctures holes in human cell membranes in order to damage the cell). Alpha toxin is what cause the sometimes fatal toxic shock syndrome. Many other common bacteria also have their own pore forming toxins.
Many bacteria posses SUPERANTIGEN toxins, which can precipitate profound inflammatory responses. Usually these superantigen-initiated inflammatory responses are designed to misdirect or thwart our immune response, in order to aid bacterial survival. This is an example of IMMUNE EVASION. Though because of this bacterium's need to survive, and its deployment of superantigens to serve its survival purpose, we end up with an inflammatory diseases like MS or arthritis. Hardly a symbiotic relationship.
Clostridium difficile (which has been associated with autism), secretes a toxin that increases the activation of the nitric oxide receptor (nitric oxide is an important neurotransmitter). Clostridia bacteria also have an enzyme that reduces nitrate to nitrite. So their presence in the body introduces two factors that can alter nitric oxide physiology. Alterations in nitric oxide physiology can have a profound effect on brain function.
Heat-stable enterotoxins are another toxin that can activate nitric oxide receptors. Bacteria that secrete heat-stable enterotoxins include: Klebsiella pneumoniae, some strains of Escherichia coli, some strains of Staphylococcus aureus.
And this just scratches the surface of how the numerous toxins and enzymes secreted by bacteria can dramatically alter human metabolism.
For more info on the way bacteria can modulate human metabolism, you might want to do some research on bacterial ENDOTOXINS, EXOTOXINS and ENTEROTOXINS. And bacterial IMMUNE EVASION strategies.
With the repeated references to "Bacteria-free animals"
Reply | Report Abuse | Link to this"lacking normal gut microflora" "normal gut bacteria" "microbe-free animals" anyone reading this would assume that all bateria, gut microflora and microbs are bad and have a negative impact on behavior. This of course make no sense and therefore the study needs to be specific as to what comprises "a normal bacterial environment". This is yet another inexcusable over-generalization of what is a very complex system without any regard for the many different variables that comprise it.
I found this article quite interesting. The association of the flora balance in our gut has been considered a factor in those who are diagnosed within the Autistic spectrum. Maybe then the development of the brain during growth is affected by the bacteria we have inside our gut. Question I have is: can these bad bacteria be transferred through mothers milk? It makes sense that they can after all we get the good bacteria from mothers milk. If the mother has gut problems and is feeding her new born child could that transfer those bacteria to the child as well causing the bacteria balance in the gut to tip in favor of the bad bacteria. This imbalance could contribute to or "kick start" a dormant condition. Could this be why Autism is not apparent in a child until they are older than 4 years of age?
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