Gut-Brain Health – What Neuroscientists Are Calling “A Paradigm Shift”

In November 2014, members of the Society for Neuroscience (SFN) held a symposium titled Gut Microbes and the Brain: Paradigm Shift in Neuroscience. A summary paper of emerging topics covered in the symposium claimed,

“…the discovery and the explosive progress in the characterisation of the gut microbiome have initiated a paradigm shift in medicine and neuroscience.”

A summary of the symposium considered the growing body of preclinical literature that demonstrated a complex signalling system between the mind, brain, gut, and microbiome.

The findings resulted in speculation that alterations in the gut microbiome played a pathophysiological role in human brain diseases, including:

• autism spectrum disorder
• anxiety
• depression
• chronic pain.

John Cryan, an Irish neuroscientist working in the field, likened gut-brain communication to Downton Abbey-like upstairs/downstairs communication,

“The upstairs and the downstairs need each other to survive. From a distance, it looks like they are living completely separate and they don’t have much to do with one another. But when things start going wrong downstairs that filters on upstairs. It’s the same with the gut and the brain. If there is something wrong with your microbiome, it’s going to filter on upstairs in the brain, too.”

The microbiome is impacted by stress.

Psychological and physical stressors alter the composition and metabolism of the gut microbiota. And experimental changes to the gut microbiome can affect emotional behaviour and related brain systems.

For example, researchers observe a decrease in BDNF (a key protein involved in neuronal plasticity and cognition) in the hippocampus (a region involved in emotion, learning and memory) when they give mice antibiotics.

Tracy Bale and her team at the School of Veterinary Medicine at the University of Pennsylvania discovered that a mother’s microbiome can pass stress-induced changes to her offspring, potentially affecting the development of the baby’s brain.

In a 2015 interview with the Kavli Foundation, Bale noted,

“There are key developmental windows when the brain is more vulnerable because it’s setting itself up to respond to the world around it.  So, if mom’s microbial ecosystem changes — due to infection, stress or diet, for example — her newborn’s gut microbiome will change too, and that can have a lifetime effect.”

A role for probiotics

A growing body of evidence from rodent studies further supported a role for probiotics. Bifidobacterium and Lactobacillus probiotic treatment show beneficial effects on anxiety- and depression-like behaviour in rats and mice.

In one human study of chronic fatigue syndrome (another disorder of brain–body interaction), a randomised, double-blind, placebo-controlled trial of a Lactobacillus-containing probiotic decreased anxiety, but not depression symptoms, in the active treatment group. The study, published as a brief report, lacked detail in terms of the reported result and should be interpreted with caution.

Probiotics are being used widely (and in 2015, represented a 20-billion-dollar industry). Overall, human studies suggest potential positive effects on mood, but human work is preliminary, and the SFN symposium called for larger, well-designed clinical trials to be conducted.

A look back to 2015…

Crowd-sourcing faecal samples (yep, The American Gut Project was crowd-sourcing poo!), faecal transplants, mRNA sequencing or proteomics, fMRI … the symposium concluded that it is difficult to predict the trajectory of the next exciting period of discovery.

Will the gut microbiome add paradigm-transforming insights to our existing understanding of human brain function in health and disease, resulting in novel therapies?

Or will it represent an incremental step in understanding the inner workings of our brains?

Certainly, the next few years of research hold the potential to uncover intriguing connections between gut bacteria and neurological conditions that may possibly impact human health.

In 2015, Cryan was very enthusiastic,

“We’re right at the dawn of a whole new way of thinking about brain development and brain heath. And the neuroscientific evidence for the role of the microbiome is just getting stronger and stronger at the basic level.”

2023 Updates: what has happened in the decade since the gut-brain paradigm shift?

🌱 Scientists have continued describing the strong relationship between gut and emotional health.

Altering the gut microbiome in mice changes the connectivity and cellular function of their brains, causing them to become more anxious. Mice who lack a gut microbiome have disturbed cellular structure of their prefrontal cortex, an area of the brain that is involved in emotions and cognition.

Some of the experimental changes we’ve observed in mice are now also being investigated in humans. People with diverse bacterial populations in their gut are more likely to have greater emotional well-being, whilst specific types of gut bacteria are more associated with altered risk of anxiety, depression and stress.

🌱 Poor gut bacterial diversity in humans is also linked to anxiety and decreased volume of grey matter in the prefrontal cortex.

Several research groups support this finding in both human and rodent studies. Researchers published a large-scale study of nearly 400 new mothers and their babies in 2020. This work found that stress during pregnancy increased gut bacteria associated with inflammation and decreased other types of healthy gut bacteria. Meanwhile, the babies whose mothers had low levels of the stress hormone cortisol during pregnancy had increases in brain health-promoting gut bacteria.

Another study published in 2023 found similar results but extended the findings also to include the first year postpartum. In this study, mothers who experienced stress, anxiety and depression anywhere from early pregnancy up to roughly a year postpartum had babies with altered gut microbiomes.

🌱 Using probiotics to improve brain health has rapidly become a popular field of neuroscience research, with these types of probiotics having now been dubbed “psychobiotics”.

Delivering probiotics to change the gut microbiome has shown promising effects in humans across a variety of diseases, from anxiety and depression to Parkinson’s disease and Alzheimer’s disease. Although we still need larger-scale clinical trials, the mounting evidence supporting probiotics for improving brain health encourages us. The development of targeted psychobiotic therapies for treating specific brain disorders is also underway by various pharmaceutical companies.

🌱 The gut-brain connection has now been implicated across many human brain disorders and diseases.

Changes to the gut microbiome are now known to play a role in the development and progression of a variety of neurodegenerative diseases, including Alzheimer’s disease, multiple sclerosis, motor neuron diseases, and Huntington’s disease.

Research has particularly exploded in recent years investigating the role of gut-brain signalling in Parkinson’s disease, with significant changes observed in both the composition of the microbiome as well as the function of the gut. Neuroscientists now even believe that Parkinson’s disease first originates in the gut up to 20 years before motor symptoms begin, with the disease later travelling up to the brain through the vagus nerve.

Traumatic brain injury and stroke are also both now known to alter the gut-brain connection. There’s even emerging evidence that the gut microbiome may affect the development and treatment of brain cancers, such as glioma.

🌱 Development of novel therapies for targeting the gut microbiome to promote brain health has skyrocketed.

The majority of therapies being investigated primarily target the gut to improve brain health. The importance of a healthy diet for gut health has spawned increased interest in research into nutritional and dietary interventions to treat brain disorders. Early case reports and preliminary clinical trials have additionally shown improvements in both the gut microbiome and neurological symptoms following faecal transplants in Parkinson’s disease, Alzheimer’s disease, motor neuron disease and multiple sclerosis patients.

Early evidence suggests that stimulating or changing brain activity may alter the gut-brain axis. For example, modulating brain activity using non-invasive repetitive transcranial magnetic stimulation or rTMS has also been shown to increase healthy gut bacteria in stressed rats. Deep brain stimulation in people with Parkinson’s disease also alters the composition of the gut microbiome. However, researchers need to conduct more studies to fully understand how brain modulation can influence the gut microbiome before they can use these techniques as potential therapy.