From: gemini23x@gmail.com   
      
   FEATURES  BIOLOGY 08 SEPTEMBER 2016    
      
   Mood, mind and memory: can gut bacteria meddle with the brain?    
      
   We may think our grey matter is isolated from the effects of germs living   
   inside our intestines. But, as Dyani Lewis writes, mounting evidence – at   
   least in animals – shows this isn't the case.    
      
      
   Links between the microbiota and psychological disorders such as depression   
   and anxiety have, for the most part, only been shown in rodents.    
   RICHARD WAREHAM FOTOGRAFIE / GETTY IMAGES    
   This is the fourth part in our series on the microbial populations we harbour   
   and their effects from brain to bowel. Check out the previous instalments:    
   Microbes and you: a partnership millions of years old    
   How bugs in your gut can make you fat (or thin)    
   Microbe tenants help – and hinder – your immune system   
      
      
   The microbes in your gut may be tiny, but their influence appears to extend as   
   far as the brain, affecting mental health, stress levels, memory and cognitive   
   abilities. Yet many of the most compelling results illustrating the   
   microbiota-gut-brain axis,    
   as it has become known, have only been seen in animals.    
      
   The potential for gut microbes to affect mood is probably best illustrated by   
   an experiment conducted at McMaster University in Canada. Mice devoid of a   
   microbiota were effectively given ‘personality make-overs’ via poo   
   transplants. Timid mice became    
   more brazen, and once daring mice retreated into shyness, taking on the   
   anxiety profiles of their donors.    
      
   Human-to-rodent poo transplants also work. When researchers at University   
   College Cork in Ireland fed rats poo from people with depression, the rats   
   became depressed and anxious.    
      
   In humans, a handful of studies link changes in the gut microbial ecosystem to   
   our mental health. Anxiety levels in patients with inflammatory bowel disease,   
   for instance, track with the level of disruption to their gut microbial   
   communities. Altered gut    
   microbes, as well as gastrointestinal symptoms – such as constipation,   
   diarrhoea and inflammation – are also common in autism spectrum disorders.    
      
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   Scientists are still nutting out the possible mechanisms behind these   
   long-ranging effects, and have found several possible communication channels   
   between the gut and brain.    
      
   The first is via neurotransmitters – chemicals that relay messages between   
   nerve cells. Many of these chemical messengers are made by the brain and other   
   neural tissue. But some, including serotonin (and its precursor tryptophan),   
   norepinephrine and    
   dopamine are also synthesised by gut microbes.    
      
   When the University College Cork team treated mice with the probiotic   
   Lactobacillus rhamnosus, they saw levels of a lock-and-key partner of one   
   neurotransmitter – GABA – rise in some brain areas and drop in others. The   
   mice were also less depressed,    
   less anxious and less prone to stress.    
      
   But whether tinkering with the gut ecosystem in humans translates into changes   
   in neurotransmitter signalling in the brain – much less the behaviours they   
   affect – is still largely a mystery.    
      
   Another communication highway between gut and brain is the vagus nerve. The   
   vagus nerve connects the base of the brain (the brainstem) to the gut – as   
   well as the heart and lungs – and controls a bunch of unconscious tasks,   
   such as regulating heart    
   rate, squeezing food through the gastrointestinal tract, and sweating. It also   
   relays stress response signals back to the brain.    
      
   Research in mice suggests that when the vagus nerve is severed, a crucial line   
   of communication between gut and brain is taken down. In the study of mice fed   
   the probiotic Lactobacillus rhamnosus, the beneficial effects of the bacteria   
   – lower levels    
   anxiety, depression and stress – disappeared when the vagus nerve was cut.   
   But it’s still a mystery how the vagus nerve works to relay messages from   
   the gut to the brain.    
      
   The leaky gut phenomenon also makes an appearance in the microbiota-gut-brain   
   axis. When there are fewer beneficial microbes to spit out short chain fatty   
   acids, the lining of the intestine – usually firmly glued together and   
   protected by a thick layer    
   of mucous – becomes permeable to bacteria and other by-products of digestion   
   that wouldn’t normally leave the confines of the gut.    
      
   IT IS ENTICING TO THINK PROBIOTIC SUPPLEMENTS TO TREAT PSYCHOLOGICAL DISORDERS   
   – DUBBED 'PSYCHOBIOTICS' – COULD ONE DAY HIT THE SHELVES.    
   This leakage can ramp up inflammatory signals around the body, including in   
   the brain, and could be one source of the chronic, low-level inflammation seen   
   in people with depression.    
      
   A leaky blood brain barrier may also be part of the picture. The short chain   
   fatty acids that help to maintain the gut barrier play a similar role   
   maintaining the highly selective membrane that protects the brain from bits   
   and pieces in the bloodstream.    
      
   Germ-free mice have a leakier blood brain barrier than conventional mice. But   
   a Swedish team at the Karolinska Institute found that when fed poo from   
   conventionally raised mice, or a selection of microbes known to churn out   
   short chain fatty acids, the    
   blood brain barrier becomes less leaky.    
      
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   Fast food diets have been linked to leaky gut and depressive symptoms.   
   Unsurprisingly, diets rich in fruits, vegetables and fish tend to decrease   
   depressive symptoms.    
      
   These dietary studies raise the question of whether behaviours seen in mice   
   – and perhaps in humans, too – could be the result of what’s happening   
   in the gut, rather than just the brain. They also beg the question of whether   
   rectifying disturbances    
   in the gut ecosystem could improve symptoms.    
      
   In mice, the evidence is promising but mixed. Bacteroides fragilis – a   
   microbe known to protect against gut inflammation – plugged the leaky gut,   
   restored microbiota to normal and reduced autistic-like behaviours in mice   
   with an experimental form of    
   autism, even those fully grown.    
      
   But a study of a different mouse model of autism using a different beneficial   
   microbe found that adding back the depleted microbe could restore some, but   
   not all, of the behavioural deficits.    
      
      
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