The gut-brain link promises new paths in autism research and treatment

In trying to understand the behavior of people with autism, health care professionals and researchers have long focused on the brain dysfunction of these individuals. New research reveals that gut health could be a key piece of the puzzle. Studies show gene mutations found in both the brain and the gut could be associated with the chronic digestive and social difficulties people with autism experience. This same gut-brain nervous system link could also provide clues for developing treatments to ease autism symptoms.

How is the brain connected to the gut?

The gut and the brain have many neurons in common. The gut is controlled by the enteric nervous system, part of the autonomic nervous system. The enteric system is sometimes called the "second brain." Many of the chemicals and cells it uses are the same as those in the brain, and the gut and brain talk to each other constantly. This gut-brain link in children with autism can manifests as nausea and abdominal pain when they're in stressful situations. A study recently found identical mutations in cells in the brain and the gut. This discovery suggests that behavioral issues and gastrointestinal difficulties in persons with autism may have the same origin. A mutation related to autism that affects neuron signaling in the brain also causes problems in the gut. The results were first described by Christopher Gillberg et al. in 2003. Gillberg and his team studied two brothers, looking for DNA matches. These researchers were the first to attribute a neurodevelopmental disorder to a gene - specifically the NLGN3 and NLGN4 on the X chromosome. Investigators at RMIT University built on Gillberg's research by studying mice with the same mutation. The team found that this variation impacts gut contractions and the speed at which food moves through the small intestine. It also determines the number of neurons in the gut. In addition, the mutation affects the microbiome, bacteria that are essential to proper gut function. A Caltech team led by Sarkis Mazmanian transferred gut microorganisms from children with autism into mice grown in a "germ-free" environment. Samples from persons without autism were transplanted into other animal groups as a control. After the transplants, the mice that received microbiota from subjects with autism developed behavioral differences that looked a lot like autism. The mice in the control group did not. The mice that received microorganisms from children with autism also showed lower amounts of the chemicals taurine and 5-aminovaleric acid (5AV), which affect some neural receptors. The team also checked to see if restoring taurine and 5AV to normal levels would reduce autism-like behaviors. They treated mice that had shown autism-like behavior with 5AV and taurine. Autism-like behaviors decreased! When the researchers looked further, they found that 5AV, in particular, was responsible for the neural response changes.

From mice to men

Approximately 40% of children with autism deal with digestive difficulties such as diarrhea and constipation. In a small study involving 18 children on the autism spectrum who had these problems, both digestion and behaviors improved after treatment with gut bacteria from healthy people with no symptoms of autism. This experiment used no control group, so more research is needed before doctors can consider recommending this therapy. A review of 150 papers supports the idea of a gut-brain connection in autism. In addition to the neurological and mutational experiments with mice, some research suggests that bacteria in the gut may produce toxins that make the intestinal lining more permeable. This leakiness could allow potentially damaging substances to travel through the bloodstream into the brain. While some literature suggests that problems with the gut cause autism, that remains unclear. A leaky gut may make autism symptoms worse.

Therapies that target this connection

Li et al. identified several strategies that modulate gut microbiota that have shown promise in treating people with autism. The authors site numerous studies to support these interventions.

• Probiotics
• Pre-biotics
• Fecal microbiota transplantation
• Micro biota transfer therapy
• Antibiotics
• Diet - specifically, gluten-free, dairy-free and kytogenic diet.

Of course, researchers will continue to investigate how mutations in the nervous system affect the gut and how tweaking gut microbes could improve mood and behaviors. Mazmanian's team is studying which receptors on the brain control reactions to taurine and 5AV. The researchers are also testing other small molecules and microorganisms as treatments in autism-model mice. While autism research on mice doesn't always translate to humans, it can still be promising. Further studies on the gut-brain connection promise to continue improving the medical community's understanding of autism and pointing the way toward better treatments. Contact Therapeutic Options for more information on autism therapies.