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.
Consistent with these behavioral findings, two genes implicated in anxiety -- nerve growth factor-inducible clone A (NGF1-A) and brain-derived neurotrophic factor (BDNF) -- were found to be down-regulated in multiple brain regions in the germ-free animals. These changes in behavior were also accompanied by changes in the levels of several neurotransmitters, chemicals which are responsible for signal transmission between nerve cells. The neurotransmitters dopamine, serotonin and noradrenaline were elevated in a specific region of the brain, the striatum, which is associated with the planning and coordination of movement and which is activated by novel stimuli, while there were there were no such effects on neurotransmitters in other brain regions, such as those involved in memory (the hippocampus) or executive function (the frontal cortex).
When Pettersson’s team performed a comprehensive gene expression analysis of five different brain regions, they found nearly 40 genes that were affected by the presence of gut bacteria. Not only were these primitive microbes able to influence signaling between nerve cells while sequestered far away in the gut, they had the astonishing ability to influence whether brain cells turn on or off specific genes.
How, then, do these single-celled intestinal denizens exert their influence on a complex multicellular organ such as the brain? Although the answer is unclear, there are several possibilities: the Vagus nerve, for example, connects the gut to the brain, and it’s known that infection with the Salmonella bacteria stimulates the expression of certain genes in the brain, which is blocked when the Vagus nerve is severed. This nerve may be stimulated as well by normal gut microbes, and serve as the link between them and the brain. Alternatively, those microbes may modulate the release of chemical signals by the gut into the bloodstream which ultimately reach the brain. These gut microbes, for example, are known to modulate stress hormones which may in turn influence the expression of genes in the brain.
Regardless of how these intestinal “guests” exert their influence, these studies suggest that brain-directed behaviors, which influence the manner in which animals interact with the external world, may be deeply influenced by that animal’s relationship with the microbial organisms living in its gut. And the discovery that gut bacteria exert their influence on the brain within a discrete developmental stage may have important implications for developmental brain disorders.
ABOUT THE AUTHOR(S)
Robert Martone is the Neuroscience therapeutic area lead for The Covance Biomarker Center of Excellence located in Greenfield, Indiana. He is a research scientist with extensive experience in drug discovery for neurodegenerative diseases.
Let's see. New York city was good. We actually only made it to Manhatten. Next time we plan on taking the directions we originally wrote and giving more than a day to see it all. We were supposed to go through Newark onto the Brooklyn bridge but ended up coming over the Peace Bridge I think. Still fun but I didn't get to buy a cheesecake like I wanted to. The reason we made a wrong direction was because I gave vinny the wheel and slept for a bit. I woke up 170 miles later in the wrong area. I managed to get us there still.
Right before we left to NYC I met up with Michelle. Real nice girl I used to work with. Texted me and said she was bored and I texted back "Okay how bored? And do you want to hang out?" So she was there with intention. I got the response of "Very, haha, and yes" So I told her I would get ahold of her when we got out of the movies. Which I did. We went to some diner because a lot of things are closed around here late at night. Had to take Vinny with me since we were so close to leaving and no point in separating. We had to meet at work because Michelle isn't very good with directions. Surprising for co-workers*. We talked and joked for a while, 12 to almost 2 in the morning. I'd say something stupid or just busting her chops she would shy away and say "I hate you" or "I hate you so much" in a playful way. Then we departed and i was on my way to the City. Coffee on Friday hopefully.
*note it was rumored that Michelle had a thing for me which wasn't apparent until they saw us show up at work off of our shift together. Mel told me it seemed obvious now because she was always saying how "Karl and I are supposed to go to dinner!" for about two weeks and when she came in the back she was always asking if I was in, or brought up to Mel if we did anything lately. (Melanie is pretty much my best friend at this point. Like literally haha). So there was that rumor that she digs me. And I can't say it is a bad one because I kind of do too!
First court date yesterday. That was a reschedule for this Friday. :/ Oh boy. It is a hardship hearing so I don't know. High hopes? Wish me luck?
Tuesday. I got back from the movies by myself. I wasn't drunk. Or high on caffeine. But I had large amounts of both in the past few days with minimal sleep. So when I got home I couldn't sleep but my head just fell to the pillow. I could feel all the caffeine and alcohol leaving my system. My head was heavy and in pain. My body in shock. I needed a way out but I didn't have the will or power to get up and get an aspirin or go somewhere calming. I laid there. I don't know when I passed out but I did and slept for about 8 hours. Best sleep I had all week. Mostly running on short bursts of 20 minutes to an hour or just 4 hours. Super
It is now 12:06, coffee is made. Do a short workout then I am on the road again for a little while. Any questions? Otherwise let's talk.
I look to my left. There is a cat on my jacket. Ew.
Today was nothing special, just another Wednesday. In women & mass media, we discussed anime and the stereotypes there in. I haven't watched anime myself, but it was still an interesting discussion. It ended up evolving into a conversation about Western cartoons since most of us hadn't had much exposure to anime. It's strange to look back on cartoons from my childhood and to realize that I was receiving all kinds of messages about gender roles that I wasn't aware of, but was still picking up on. In Spanish I spoke Spanish, and in experimental methods I took notes about designing a survey. It was all pretty obvious stuff, but I took notes using the new markers I recently got to make my collage for sexualities, so I had fun with it. I'm busting my ass in stats trying to keep up with what's going on, and I'm doing well so far. We had a quiz today that I basically aced, which is great. It boosts my confidence. Right now I'm working on finishing up my paper for sexualities. It's been pretty easy because it's basically an inference and opinion paper. There's really no getting it wrong.
I talked to my mom earlier this evening and she's really excited to see me, which is really nice. I kind of like that I haven't see my family in like five months because it means they're really genuinely going to be happy to see me and they're going to be sure to spend time with me since they realize I'm not around often anymore.
My brain is going crazy lately trying to finish up all the last minute assignments and tests before the end of the semester/getting ready to visit Carlsbad/preparing to move (we get our keys tomorrow!)/studying for finals/ectectect. It never ends. We haven't even started packing or anything, but I think we're going to bring some stuff over to the new apartment on Thursday . Then on Friday we're going to clean up this apartment. That way we'll have a start before we go to Carlsbad and we won't feel so totally overwhelmed when we get back.
Went to a party related to work. It wasn't a boring one at that. They call it white night because at work we always have mexican food. But on white night we have food that white people like (or originated or whatever). It was really fun.
Since mel and I are carpoolers she came with me and all. I was driving so I didn't drink. I only have several glasses of wine when I first got there. It wasn't much considering I was there for 5 hours. Plus I think when my sister and I can split a bottle of Jack Daniels and be fine is something else. Solfina was pleased that I was there I hear. Her daughter Terisita told me today. Haha. She said I looked like Solfina's husband. That was long ago. But it was flattering I must say. He was a strapping gentleman.
Mel was a little past. and I had to take her home. There was a little mix up or something between her and some of the other people. I pulled up the car and helped her to it. She was a little sleepy on the way home. We got to her place. I grabbed both of her bags and went to the portch. A two story house that rents to several people. I took out the keys and put them into my pocket. I went back to the car and helped her to the portch. I helped her sit on one of the chairs. And told her I would be right back. I went upstairs and got her dog, Maddison. I gave Maddison water and then took it outside to go to the bathroom. Mel was still on the portch and one of the other borders came out to talk to her a bit. After I took care of the dog I went to return him to his room (maddison.) I got a glass of water for Mel because it is always good to have a little water if you have had been drinking. She was hungry so we went around town to find some place to eat. We ended up at a bar where we ordered food. I wasn't severely hungry or had a lot of money on my person. o get there thoShe kept telling me that she was going to die. That she was going to be run over. I had to disagree with her I said because I told her that I had her and that she could lean on me. She ordered an appetizer because she couldn't decide. The ones where you sample about every other appetizer. She said I could have some. We shared. She orded a beer. We did share a deep conversation though. It was very touching even for me. But long story short. We went back to my car. Made a few phone calls. I left my cellphone at my bosses house, Donna. Mel and I went back to her house. She looked at me and asked if I wanted to watch a movie. Obssesed. Heh, I said yes. I never saw it before. We went into her place. Ordered it on the cable. So we watched it. Melanie fell asleep slightly early. I watched a little more of it. I layed on her bed. I looked over at her.She was sleeping. Very peacefully. Slept like an angel. It was cute. I thought it was a good of time as any to leave. I looked up at the cchuckled to myself. I leaned over Melanie and looked at the time. I got up and got my penny loafers and whispered good night. I wrote a note and left it in her kitchen. Vague. But longstory short it was just a reminder for the next day. I patted Maddison on the head. I got home at 3:30 at night. I had a beer and ate something because I hadn't eaten in about 5 hours besides finger foods.