“The E. coli made me do it.” – Bacteria and Behaviour by guest blog author Katsiaryna Dalidovich.
In a recent The New Yorker article, James T. Rosenbaum – Professor of Ophthalmology, Medicine, and Cell Biology at Oregon Health and Science University – reviewed the research suggesting that E. coli and other bacteria may cause depression, anxiety, and other mental illnesses in humans, by altering our brain chemistry. This really makes you wonder, ‘Just how much influence do our microbes have on us?’
A lot has changed since DNA structure was first described in 1953. At that time our genes were regarded as our biological destiny. We now realize that human genes are outnumbered 150-fold by the non-human genes in and on our bodies. These belong to the collection of bacteria, viruses, fungi, and other microbes that share our bodies, and outnumbering our own cells ten to one.
Exploration of all the metabolic intermediates in human metabolism is not yet complete. So where do we start our search for the contribution of the ‘foreign’ metabolites produced by our inner ecosystem? What is their role in human health and illness?
In 2008, the first stage of the Human Microbiome Project pioneered research on human microbial species. The project resulted in a vast number of findings. One of the most interesting suggested that gut bacteria may alter our brain chemistry affecting our moods and behaviour.
Bacteroides fragilis and autism
Autism is a complex spectrum of neurodevelopmental disorders with classic features:
— impaired communication
— poor social engagement
— repetitive behaviour
Interestingly, autistic children are over 3.5 times more likely to experience GI problems.
Trying to investigate the “tummy problems”, Arizona State University scientists found that autistic participants had greatly reduced diversity of gut bacteria. So what is the role of gut bacteria in autism?
Researchers at Caltech conducted research on mice models of autism. The pups went on to develop “leaky gut,” — a condition often seen in autistic children. On analysis, scientists found that the blood of autistic mice contained 46 times more 4EPS, than that of the control group (4EPS is a molecule produced by an as yet unidentified strain of gut bacteria). What is more, injecting healthy mice with 4EPS made them more anxious. A similar molecule has been found at elevated levels in autistic patients.
A second finding revealed that “autistic” mice had lower levels of Bacteroides fragilis in their guts compared to the control group. Additionally, after feeding them with B. fragilis, their behaviour and gastrointestinal health both improved.
Steve Collins and his group at McMaster University have done studies where they have shown that transplanting the microbiota from an animal with an anxious phenotype into a germ-free animal gives that animal an anxious phenotype; and likewise, transplanting the microbiota of an animal with a depressive phenotype into a germ-free animal renders that animal depressive.
Gut–Brain Axis Pathways
There are a number of ways our gut bacteria communicate with our brain. The Caltech researchers demonstrated an endocrine pathway, in which involved metabolites from gut bacteria leak into blood and reach our brain affecting its function. The McMaster University researchers speculated that the changes they observed were mediated by gut bacteria indirectly influencing metabolism of their human host’s neuroactive chemicals and their precursors. Other recent research has suggested many more possible pathways by which our gut microbiota communicate with our brain.
Could the microbes that inhabit our guts help explain that old idea of “gut feelings?”
There is a lot of pre-clinical data generated from animal models of depression, anxiety and other behavioural disorders. Researchers identified that certain strains of bacteria or certain psychobiotics are effective in treatments of those pathologies. However, a number of questions have to be answered before clinical trials can take place. These are:
- Does our microbiome cause these diseases?
- Is treatment that works in animal models safe for human?
- What are the proposed effects of such treatments?
- Are the microbes initiating or just propagating the disease?
- Are the treatments necessary, sufficient, or neither?
Katsiaryna is a year 2 BSc Nutrition student at King’s College London with an interest in nutrigenomics, gut microbes and human health.