Just as geneticist Francis Collins and his team of international researchers at the Human Genome Project embarked on their 13-year long journey to sequence the entire human genome starting in 1990, researchers across the world are now in a race to sequence the genomes of the millions of strains of bacteria present in our guts.
They’re looking to unlock the mysteries of several diseases for which we are yet to fully understand the cause. But these diseases are increasingly being linked to a dysbiosis of the gut (imbalance in gut microbes.) This is also driving the search for new drugs in the form of probiotics, especially ones that can tackle neurological and psychological disorders.
Hunt for psychobiotics
Several groups globally have begun the hunt for psychobiotics – probiotics that can confer mental health benefits when ingested – and are looking to identify specific strains of bacteria that can target the gut-brain axis, the two-way biochemical signaling pathway between the gut and the brain.
The general idea is that when the flora in the gut goes out of whack, it causes chemical and other imbalances that are manifested as disorders. If we can bring back this balance by either ingesting these microbes or making our gut a conducive environment for them to flourish, then we can better control medical outcomes.
With over 300 million people globally suffering from depression and anxiety, it’s little wonder that scientists have set their eyes on developing new-age treatments for such disorders. While established treatments for such psychological disorders already exist, they don’t work fast, and none are without side effects.
“The basis for most studies on psychobiotics is to target the gut-brain axis,” says Mojibur Khan, a scientist at the Indian Institute of Advanced Study in Science and Technology (IASST), who has been studying the gut microbiome for over a decade now and has worked on developing next-generation probiotics. “The way to understand it is that some live and dead microbes have been found to act on this gut-brain axis, and studies using these have shown promise in improving psychological and neurological complications in both animal and human models,” he adds.
According to Khan, it’s still early days for such research since we don’t fully understand the mechanisms in which the trillions of microbes in our guts influence the brain. However, our knowledge in the space is growing exponentially with each passing day and it’s only a matter of time before there are significant breakthroughs. The global community of researchers concurs with this view, stating that the underlying interaction pathway has not been completely elucidated, but clinical outcomes in ongoing studies are highly promising.
There’s strong evidence to show the link between the neural, endocrine, immune and metabolic systems and the gut. There are three possible ways this could happen, according to researchers at the Monterrey Institute of Technology and Higher Education in Guadalajara, Mexico, who did a systemic analysis of several studies on psychobiotics.
The first theorised mechanism is that gut microbes act on the hypothalamic-pituitary-adrenal (HPA) axis – the central stress response system. Second, they could be directly acting on the immune system. And third, they can alter psychological factors by secreting neurotransmitters, proteins and short-chain fatty acids.
“…the consumption of psychobiotics could be seen as a viable option to both look after and even restore any damages done to our mental health…without undesired secondary effects,” the authors of the study done at the Monterrey Institute of Technology and Higher Education wrote in a paper that was published in December 2020 in the journal, Nutrients. “Especially because psychobiotics belong to microbiota naturally found in the intestinal tract, they may offer a lower risk of allergies and less dependence than psychotropic drugs,” the researchers added.
Shrilakshmi Desiraju, a researcher, and pioneer in the probiotics space who co-founded Triphase Pharmaceuticals, says that gut bacteria produce short-chain fatty acids such as acetic acid, lactic acid, propionic acid and butyric acid, apart from anti-microbial peptides that combat infections. But the reason why probiotics are being seen as a potential therapy for psychological and neurological disorders is that certain strains of bacterium in the gut have been linked to the metabolisation of the essential amino acid tryptophan, which is linked with the production of the neurotransmitter serotonin.
The gut microbiome is the largest producer of the chemical Serotonin which is responsible for states of anxiety, depression, anger, and agitation. This is possibly why depressed persons are seen to crave chocolate more than normal, as chocolate has a high content of tryptophan, the precursor of serotonin.
Serotonin also plays an important role in regulating the digestive and sleep cycles.
Moreover, probiotics have been used for decades and their safety has already been validated, but to be used as treatments or co-treatments for mental health disorders, the clinical safety and efficacy for each strain of bacterium will need to be established, says Desiraju.
“While it’s been clinically proven that the gut and brain are connected, it will take some more time to establish probiotics as therapies for neuro-related diseases because you can’t see the outcomes immediately in clinical trials,” she points out. “We’re only scratching the surface and establishing the gut-brain axis. Unless you have a full biosynthetic pathway of the way these bacteria are functioning, claims cannot be made for that strain.”
A big unknown
Just as the Collins’ team at the Human Genome Project went in blind without fully understanding the uses of sequencing the human genome, researchers today working in the field of gut microbiome and next-generation probiotics aren’t fully sure what the work will yield. It could be the basis of a new way we treat diseases, but there’s a big unknown.
“The problem is that you have a billion strains of bacteria and it’s very difficult to tell which is the pathological strain,” says Dr Raj Vigna Venugopal, a gastroenterologist and hepatologist at Manipal Hospital, Bengaluru. “In the future, this might be a very promising thing, but as of now in the clinical practice, we’re not looking at it in a big way.”
For Venugopal, until there’s more evidence and clinical trials to show that products such as psychobiotics are safe and efficacious, and the mechanism in which the link between the gut and brain is better understood, such treatments will remain out of mainstream clinical practice.
The broad consensus, for now, is that this is the right direction to keep moving in. Cheaper and faster sequencing techniques and an evolving understanding of the gut-brain axis are speeding up research into the gut microbiome. This could set the stage for future therapies that are gentler, faster acting and address disorders at the root.