From: mha23x@gmail.com   
      
   Is It the “Terrible Twos”? Or Is It a Disrupted Gut Microbiome?    
   on FEBRUARY 7, 2017    
   by CHRIS KRESSER    
   23 comments    
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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.    
      
   terrible twos    
   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    
   uminococcaceae 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).    
      
      
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