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Is It the “Terrible Twos”? Or Is It a Disrupted Gut Microbiome?

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Kids out of control? New evidence suggests that a disrupted gut microbiome could be partly responsible for unruly behavior in children. Read on to learn how the brain develops, the role of the gut in this process, and how bad temperament in early childhood might be associated with gut dysbiosis.

Leaky gut in toddlers may be the deeper explanation behind temper tantrums.
If you're a parent, this may be a familiar scene. But there may be more to the "terrible twos" than meets the eye. istock.com/ShutKatya

Parents often complain about the “terrible twos,” which more often than not turn into the “terrible threes and fours.” Ritalin is one of the most prescribed drugs to children, and the number of prescriptions doled out for attention-deficit/hyperactivity disorder (ADHD) is increasing each year.

Beyond just attention and ability to focus, temperament also includes characteristics like introversion and extraversion, self-control, adaptability, intensity, and mood. Ratings of temperament in early childhood are good predictors of personality, behavior, and risk for psychopathology in later childhood, adolescence, and adulthood (1).

Previous articles on my blog have covered the basics of the gut–brain axis and how microbes can control food cravings. In this article, I will focus on how microbes might influence temperament in children, though much of what I will cover applies to adult behavior as well.

The Developing Brain

The development of a child’s brain lays the foundation for all future behavior and learning. In the first few years of life, an estimated 700 to 1,000 new synapses (connections between neurons) form every second (2).

After this period of rapid growth and proliferation, the number of synapses is reduced via a process called pruning. During pruning, specialized immune cells of the brain called microglia break down synaptic material. This allows other connections to be strengthened and become more efficient. Studies have shown that pruning by microglia is essential for normal postnatal brain development (3).

The interaction of the child’s biology with his or her environmental conditions and experiences is what ultimately determines which connections are maintained. A synapse that is constantly activated will tend to be strengthened, while a synapse that never receives input will be pruned. In this “use it or lose it” fashion, the brain is extremely malleable during this critical period.

Could a disrupted gut be to blame for your toddler’s tantrums?

How the Gut Controls Maturation and Function of the CNS

What would happen to this process if you took away your gut microbes? Researchers in Germany sought to answer that very question. Using germ-free mice, they found that compared to conventional animals, mice lacking a gut microbiota exhibited abnormal microglial function and had abnormal development of the central nervous system (4).

The researchers wondered if microbial metabolites could be involved. The gut microbiota are constantly processing fermentable fibers from the diet and producing a wide range of metabolic end products, including short-chain fatty acids (SCFAs). SCFAs are known to be absorbed into circulation and influence host physiology by binding to free fatty acid receptors (FFARs) on cells throughout the body (5). Following this thread, the researchers genetically engineered mice to lack FFAR2 and found that these mice had similar microglial defects to those found in germ-free animals. They concluded that microbial metabolites are essential to microglia maturation and function (4).

Gut Microbiome Composition Is Associated with Temperament in Early Childhood

A group of researchers at Ohio State University wanted to determine how human gut microbes might be associated with behavior in early childhood. They studied 77 children between the ages of 18 and 27 months. Ratings of temperament were provided by the mothers of the children using a standardized questionnaire, and fecal samples were collected from the children’s soiled diapers for microbial DNA sequencing (6).

The results of the study, published in 2015, were quite interesting. For both girls and boys, higher surgency/extraversion scores were associated with greater genetic diversity of microbes. In boys, higher sociability scores were also associated with greater microbial diversity. As the authors of the study explain, “the surgency/extraversion scale reflects a trait aspect of emotional reactivity characterized by a tendency towards high levels of positive affect, engagement with the environment, and activity.” Higher surgency/extraversion scores in children have previously been associated with lower depressive symptoms (1).

The researchers next wanted to look at specific groups of bacteria to see if there were any “bad behavior bugs.” They observed significant correlations between relative abundance of bacteria in the Rikenellaceae and Ruminococcaceae families and the Parabacteroides and Dialister genera and temperament. While it is unknown whether this relationship is causal, the researchers hypothesized a connection between the gut microbiota and the HPA axis.

The HPA Axis, Leaky Gut, and Temperament

The hypothalamic–pituitary–adrenal (HPA) axis is an area of particular interest in relation to temperament. Studies in animal models suggest that early life exposure to mild or moderate stressors enhances HPA regulation and promotes lifelong resilience to stress. In contrast, exposure to extreme or chronic stress early in life can induce an over-reactive HPA axis and encourage vulnerability to stress throughout the lifetime (7). Changes in the function of the HPA axis have been linked to temperament in several studies (8, 9).

Notably, germ-free mice show an exaggerated HPA response compared to conventional mice, an effect that can be partly corrected by reintroduction of a microbiota, but only at a very early stage (10). If you’re an avid reader of my blog, you’ve probably already heard me talk about leaky gut. When the gut barrier is compromised, bacterial components and other materials from the gut lumen (endotoxin) can leak into the bloodstream. It turns out that endotoxin is a potent stimulator of the HPA axis, causing prolonged activation (11, 12).

We can now see clearly how gut dysbiosis and intestinal barrier disruption can lead to abnormal HPA function and behavior. Nonetheless, this is just one of many potential connections between the gut microbiota and temperament. We’ll explore a few more in the next section.

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Other Mechanisms: Neurotransmitters and the Blood–Brain Barrier

In addition to regulating the immune system in the maturing brain, the gut also manufactures neurotransmitters throughout the lifetime. More than 90 percent of your body’s serotonin and 50 percent of your body’s dopamine are produced in your gut, along with about 30 other neurotransmitters (1314).

The gut microbiota has also been shown to regulate the production of myelin in the prefrontal cortex, a region that is important for self-control and executive function (15). Myelin is like “insulation” for neurons, helping them to properly conduct electrical impulses.

Antibiotics provide another way to study the role of microbes in CNS function. Antibiotic-induced microbial dysbiosis in mice has been shown to impair cognition and decrease anxiety. Depletion of the gut microbiota from weaning onwards altered components of the tryptophan metabolic pathway and significantly reduced oxytocin, vasopressin, and brain-derived neurotrophic factor (BDNF) expression in the adult brain (16).

Lastly, the gut microbiota is essential for the maintenance of the selectively permeable blood–brain barrier. Just like in the gut, tight junction proteins between epithelial cells maintain the integrity of this barrier and prevent large molecules from entering the cerebrospinal fluid that encases the brain. Studies have shown that germ-free mice have reduced expression of these tight junction proteins and increased blood–brain barrier permeability (17). A compromised blood–brain barrier can easily lead to neuroinflammation and altered behavior.

Healthy Gut, Happy Child

While there are certainly many things that influence a child’s behavior, the collective body of research in this area suggests that the gut microbiota may play an important role. Cultivating a healthy gut flora for your child may not only improve his or her behavior in the short term, but will also reduce the chance of mental health issues later in life. Here are a few ways to improve your child’s gut health:

  • Probiotics or fermented foods
    In several studies, probiotic bacteria have been shown to reduce anxiety and depressive-like symptoms (18, 19, 20). One study in rats even found that probiotic supplementation reduced leaky gut and attenuated the HPA response to acute psychological stress (21).
  • Prebiotics
    Specific groups of microbes break down prebiotic fibers to form beneficial metabolites. Many microbial metabolites are small enough to penetrate the blood–brain barrier (2223) and influence brain chemistry. Butyrate, for example, has profound effects on behavior and mood (24).
  • Remove inflammatory foods and include bone broth in your child’s diet
    Healing the gut lining is essential to reducing gut and systemic inflammation that in turn can affect the brain.
  • Avoid antibiotics unless absolutely necessary
    Most ear infections and upper respiratory infections are viral and are not influenced by antibiotic treatment. If your child does need antibiotics, see my steps on how to mitigate the damage.

See my free e-book on Gut Health for more details on healing the gut.

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62 Comments

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  1. My twin daughter who was born at 28 weeks and was extremely sick and fighting for life for her first 3 months of life and being pumped full of antibiotics and copious amounts of other medications during her struggle has severe stomach issues, extreme vomiting lead to a diagnoses of lactose intolerance, she is 1 year old now, 10 months corrected age and her temperament is extremely hyped and aggressive in comparison to her twin sisters who didn’t experience the same trauma she did for the first 3 months of her precious life- is that a factor ? Has her brain development effected her personality?? I’d love more information on this please..

    • I’ve heard of a probiotic called Just Thrive which some say is impressive for children with various serious issues. You may want to look it up.

    • It’s her gut microbiome. You can fix it with diet and vigilance. I’d be careful with probiotic pills… fermenteds are more reliable. Say, a fecal transplant (docs take feces from the one, pop into the other, no cutting – from the twin might be interesting.

  2. Some of this stuff is interesting, but as DJ pointed out, it’s probably not more than just one aspect of things.

    How about the hunter/gatherer practices of prolonged breastfeeding (by comparison), carrying the child, not leaving it to sleep on its own, not leaving it to cry it out, and treating it as autonomous? How about attachment parenting? In the book The Continuum Concept, Jean Liedloff talkes about tantrum-free kids, if I remember correctly.

    Psychology professor Darcia Narvaez has put together this list:
    https://www.psychologytoday.com/blog/moral-landscapes/201701/raising-children-love-or-dynamite

    And even if we’re to focus on the gut microbiome, isn’t breast-milk a prebiotic (containing oligosaccharides)? And isn’t vaginal birthing important for planting a healthy microbiome?

    • Love your point about breastmilk and vaginal delivery! Also the hunter gatherers were exposed to good microbes in the rich soil. Our soil is now so depleted in the US due to poor agricultural practices that we are better off supplementing with fermented foods and supplements.

  3. Great article Chris. I am about to become a grandmother and thankfully all of my family understand that diet is the absolute basis for good physical and mental health. My own children were weaned onto food that I cooked myself (without salt). They were never fussy eaters, I cannot think of anything they won’t eat. We are not consumers of any processed foods and buy organic where we can afford. We handle stress pretty well and are all fit and not overweight. Contrary to this one of my oldest friends who had not been taught how to cook fresh foods had three of the most unruly children I have had the misfortune to meet. The last of the three was literally bred from conception through childhood on fast foods and frozen easy meals. I recall at the age of three this child had kicked holes in all of the doors of the house and several of the walls. That is all of the evidence I need!

    • sorry, realized this is unclear. In the paragraph leading up to footnote 16, some of us are thinking, a course of antibiotics could “increase anxiety” not decrease.

      • Hi Dana,

        The abstract from reference source 16 reads, “Gut microbiota depletion was paralleled by impaired cognition and decreased anxiety,” so I think decreased it correct.

  4. so what, kids aren’t supposed to be unruly now? every single one polite, quiet and nicely in line? to quote from below, it does seem like you’re moving into ideology and trying to connect and explain everything that you find strange with it.
    this brain-gut connexion is interesting indeed, however, kids are supposed to be unruly, too. that’s what they are. to paraphrase from one of your podcasts, it does seem like we’ve divorced from a state when we lived more in collectivity and could see what’s the norm and what’s not, how children behave, now everyone lives on their own in their home and it seems strange that, in comparison to adults, kids generally are hyperactive

    • I used to throw terrible tantrum. Could bot control my mood as a child. It was distressing for me. As an adult I have gut problems so this article makes sense. Its not about controlling kids, but if you experience this as a child you wish you had some self control back then.

      • Some children do have gut problems that would cause completely crazy behavior. On the other hand, tantrums are also sometimes the result of extreme stress that a child (being a child and having no common sense) does not know how to control. When you are 2 or 3 or 4 years old, you can’t control internal feelings of pressure (which can be caused by a lot of non-health-related things). A tantrum

        When adults experience stress, it is hoped they have the intelligence and self control to just somehow settle themselves without getting real drunk and crashing the car into a wall, or taking a knife and stabbing someone. But a young child does not have a rational brain.

        Not talking about your case in particular, but if you pick up a tantrum-ing child and hold him and restrain him and let him howl and struggle, while speaking quietly and non-threateningly, he’ll eventually quiet down and sometimes he’ll even fall asleep in your arms.

        So, sometimes it may be gut dysbiosis but not always. We have to figure out why some little kids feel so stressed that they behave in this scary manner. That you have gut issues today does not automatically mean you had gut issues back them.

      • I can see your point as well. We rarely tie bad behavior in kids to health issues. We just assume kids are just behaving badly and blame the parents for not knowing how to discipline. As adults certain medical conditions are a legitimate reason why we lash out at others or act a certain way. I want to have an open mind about this subject.

    • There’s definitely a period of learning to control the will, to choose good behaviors, etc, but it’s true that some children cannot focus or absorb what they need to because of the state of their brains, and this could literally be the cause for some.

      • true, and I completely agree, however, that’s very different from suggesting ‘bad behavior is CAUSED by diet’. kids are unruly sometimes, that’s who they are. let’s allow them to be kids without fixating on having perfect little machines

  5. Great article! You might be interested in new evidence that is suggesting that the prolific use of glyphosate (AKA Roundup) in our food supply can harm the gut microbes too via the shikimate pathway. A recent study found high levels (over the supposedly “safe” levels) in common foods that well-meaning parents often feed their kids such as Cheerios and Honey Nut Cheerios. For a complete list see this podcast and article by Dave Murphy “Glyphosate: Unsafe on Any Plate.” You can download this excellent article and graphics for free here: https://www.peakprosperity.com/podcast/105335/dave-murphy-glyphosate-unsafe-any-plate. For the health of our children and as a public health professional I am ready to start actively protesting against the use of glyphosate.

    • Hi Hilary,
      You might be interested in reading this blog article I wrote on resistant starch (a form of prebiotic): http://www.bigpicturehe. alth.com/message-to-you-from-your-friends-living-in-your-colon-please-eat-more-resistant-starch/. I think Chris also wrote an article about resistant starch. Fermented vegetables are a good source of probiotics and kids have fun helping make them. I made a three-part video series on how to make fermented vegetables. Here is a link to the first one: https://www.youtube.com/watch?v=sDepfUEkGLI. One idea with young children is to give them just a half a spoonful of the liquid in fermented vegetables per day. You can even mix it in with their other food. I hope these ideas help!

    • Hilary, I may be able to share some info on probiotic/prebiotics that would be helpful for you. Feel free to ask me for more info.

  6. Chris, do you have any resources on what to do with a toddler who might have a leaky gut (is high needs, has allergies, catches colds easily, some digestive issues) but has always had a mostly paleo diet with plenty of broth and probiotics, no antibiotics, etc.

    Can a child have allergies and a weak immune system without a leaky gut? I have always wondered this since I had my now 8 year old on GAPS for a year when he was 2, but it had no effect on his allergies or asthma. Now I am trying to help my current toddler.

    • Kathyrn, I definitely believe that a weak immune system is connected to a leaky gut. I have found it to be connected with our daughter. I believe that allergies and asthma may be connected also. If you would like to know what I have found to help, just let me know.

  7. I have little faith in a study of only 77 kids in a very narrow age bracket who potentially were eating similar foods. A broader study is definately needed to really examine what causes these types of behaviours. Sounds like the blame game and food seems to the easiest go to lately. Yes it’s easy to say we over prescribe Ritalin and other behaviour drugs in children and adults but there are many factors leading to this and food has only a part to play and is never going to be the whole picture – life just ain’t that simple.

    • I don’t think it’s “simple” — or at least not SIMPLISTIC — at all. It’s true that 77 is a pretty small study. That seems preliminary, and further study would be good. But knowing what we know about the gut microbiome, disrupting it could actually disrupt behavior through multiple mechanisms, and/or be the root behind other, previously-accepted explanations for unruly behavior.

      For instance, if junk foods like sugar are implicated in hyperactivity, a gut flora connection would help explain why we don’t see the same response from every child who eats sugar. Those with more balanced microbiomes probably adapt to a temporary spike in sugar intake better, while those with highly disrupted microbiomes have notable issues with the sugar feeding the “bad bugs.”

      We also know that a disrupted gut microbiota does, in fact, impact mental health. So the types of issues that respond to Ritalin — why could they NOT plausibly be rooted in the gut?

      Not to mention mechanisms Dr. Kresser already addressed in the post, such as disruptions to the HPA axis.

      This strikes me as more of a “common factor” than a “simple answer.”

    • I have fraternal twins – who have been offered the same diet and supplements since birth. They could not be more different in temperment! There is much to genetic factors, but we all have to do our best with what we inherit and one thing we can control is what we consume. This article helps point those of us with less robust “systems” in the right direction.

  8. Can an adult who, as a baby and young child, had projectile vomiting after bottle feedings (until about 7 months) and very pronounced startle responses, find any “cure” through Naturopathic medicine? My adult daughter has OCD about germs, anxiety, depression, chronic acne, thinning of hair and overweight. Traditional MD’s and mental health profs. Have been to no avail.

    • Absolutely! Those are ALL things tied to gut health! I went through an almost identical journey. This is caused by gut bacteria imbalances, yeast overgrowth (Candida), and leaky gut. A naturopath can get your daughter on a path to wellness by killing off the Candida, healing the gut lining, and restoring the good bacteria. Best of luck!

    • It would not hurt to start her on a Choline/Inositol supplement. You can read up on this anywhere regarding dose and a possible increase in inositol later. About the thinning hair, could that be a thyroid issue?

      Personally, this is just my opinion, but when a person has multiple challenges, it may be too difficult for them to eat a strict diet – which is what so many doctors (of all kinds) like to do. They treat people like machines instead of living, breathing, feeling people. I’m a fan of the let’s-do-this-bit-by-bit method, but then I am not a Dr.

      Best of health to the both of you. It can be a challenging, puzzling journey at times. But sometimes we get lucky. A Dr. of Traditional Chinese medicine (one who you feel comfortable with) can be helpful. The ones who speak English well (who were born here) can put things into modern medicine lingo for you if you ask.

  9. Chris, I have followed you for a couple years now and always appreciate your expertise, after that long I can’t figure out why this post is hitting me like a *eureka!* with my 3 year old son! I have 3 kids, soon to be four, my oldest (5) has a rare genetic disorder that has resulted in many many many digestive issues that after a couple years of 8-12oz a day of bone broth, probiotics, dietary restrictions and many other things we are beginning to see improvement. My trouble is buying bone broth is expensive and I love the chicken broth I make at home, (finally perfected getting my chicken broth slightly gelatinous!!) but it only makes 12 cups and lots of left over chicken. For my oldest it lasts almost 2 weeks, but for all of us it would be gone in days, what do I do with all that left over chicken?! I can’t seem to figure out how to make enough for the whole family. Anyone that has any ideas, open to hearing them!!! Thanks Chris, you don’t realize how much you have helped my family alone, I am sure many many others!!!

    • Sounds like you’re making broth from a whole chicken? You can look for farms or butchers who sell things like chicken feet or necks.

    • See if you can find a farmer/butcher who will sell you bones from grass-fed cows. They’re cheap! You can buy bones from Whole Foods as well.
      Are there families you know who consume quality meat but don’t make broth and would save you bones?

    • We buy bones from the butcher. They also have them in the freezer section at our Whole Foods.

    • You can buy just the bones from the butcher or farmer. Sometimes you can buy the bones from coops. Just start checking around but that’s what we do because we also go through more broth than meat.

    • Thanks for all the suggestions! I haven’t pursued buying bones yet, but it sounds like that’s the way to go!

  10. Hi Chris, big fan! My son is six months old and has had mucus in his diapers and G.I. problems since he was born. He had to go on anabiotic’s right out of the womb. I’ve been giving him probiotics since he came home from the hospital. I am on a diet that is free of soy, dairy, nuts, eggs, gluten, and wheat in order to keep his diapers as bloodand mucus free as possible. I preferred to do this rather than put him on formula. The G.I. doctor is saying he should move onto solids starting next month but I’m afraid that is G.I. system is too immature because he can’t even digest breastmilk properly. How can I start feeding him other things? I tried bone broth but he still hasn’t recovered from that. Apparently re beef proteins in it were too tough for his belly. Is it too dangerous to begin solid foods with such an inflamed gut? What’s the best move in the situation where I can’t seem to figure out how to reduce his inflammation and begin his healing? Thanks!

    • Try digestive enzymes, my 3 month old couldn’t digest milk protein (breastfed, but I was having dairy, not knowing that was his problem). I started giving him betaine hcl and all our problems (non-stop crying, acid reflux, etc) went away after one day! I can’t speak for what kind of enzymes would be appropriate, but do your research and find out if that may help your little one.

  11. I think “partly” should be in gigantic bold print here. There’s nothing in here concerning parenting techniques, or culture, or any of the hundreds of other factors that could, and probably do explain this transitional time period with better predictive ability.

    I feel like you’re starting to move into ideologue territory with this gut health thing. You’re talking something interesting and using it to explain everything, everywhere, at level.

    • Try a low histamine diet, which can include getting rid of a lot of inflammatory foods. The only difference I could see is not giving much or any fermented foods, as they are high histamine. Perhaps supplementing with probiotics and prebiotics would be helpful as well.
      Have you researched Mastocytosis or Mast Cell Activation Syndrome?

    • Yes, we need to know, too. I take DAO before histamine foods to avoid migraines. My son experiences a specific “tic” after eating ferments. He also got food poisoning or something a few weeks back and has been off ever since. Crazy behavior, bad gas, and a tummy ache anytime he eats meat/eggs (which he doesn’t want to). He is craving fermented foods though– so should we just let him have at it?

  12. I have a 2 year old who gets in these crying fits. Inconsolable screaming and crying. Sometimes it’s several times a day. I’ve tried a gluten free and dairy free diet but it didn’t seem to help at all. He takes a multi vitamin and a probiotic supplement. What brand of probiotic seems to work best? I’ve tried several different ones but haven’t had any noticeable improvements with them? Any suggestions on probiotics or ways to “cure” these fit would be much appreciated!

    • I’ve heard of a probiotic called Just Thrive which some say is impressive for children with various issues.

    • I take a probiotic called probio5. It actually has enzymes in it to kill off the bad bacteria and 5 strands of good bacteria. It is made so they actually make it through your stomach to your intestines. It’s helped me tremendously with being about to sleep at night and feeling more focused and less depressed during the day. It’s one of a kind!

  13. In addition to fermented foods, are there any probiotic supplements (brands, strains) you recommend for children? Thanks!

  14. The information on the developing brain is most interesting, i.e., the pruning that takes place at a certain time – though at what exact age this happens isn’t made clear.

    Also, later on in the article is this statement:

    “Antibiotic-induced microbial dysbiosis in mice has been shown to impair cognition and decrease anxiety”

    DECREASE anxiety? So then microbial dysbiosis does have an advantage? Perhaps if cognition is impaired we care less about the goings-on around us and therefore are less anxious. That is the only interpretation to be had from the above statement.

    • Maybe it’s a typo…..
      Chris I am still confused about what “prebiotics” are.
      This is so concerning I have a 7 month old and I am so scared for when the doctor prescribes her antibiotics for the first time. I took sooooooo many as a child and I think it might be a factor in causing my anxiety. I know how damaging they can be but we are all just trying to do what’s right for our children and help them be as healthy as possible how do you decide when antibiotic use is necessary and worth it??

      • Andrea,
        My son is almost 3 but I had your same fears when he was just born. I had early conversations with our pediatrician about antibiotics so when the time came it was not a surprise fight. We actually were on the same page anyway so no fight and my son turned out to have a allergy to a strain of penicillin so we have to think outside the box. I’d suggest the same for you – talk with your pediatrician. You’re a team in this. Antibiotics are so important. They have made my son well. You just have to be prudent about when to use them.

      • Andrea, my understanding of prebiotics is that they are a fiber that remains undigested until it reaches the colon where it ferments. This then feeds the good bacteria in the gut. Prebiotic foods are Jicama, Jerusalem artichoke, raw dandelion greens, raw onions/garlic, and raw banana ( I think this is the closer to green bananas and not the ripe ones).

      • Prebiotics are undigestible (to us) fiber that the bacteria (probiotics) feed on.

        So probiotics provide bacteria that may be missing, while prebiotics feed them. If you’re eating a diet of primarily whole foods, you’re almost certainly getting prebiotics through your diet.