Stellenbosch University’s research explores untapped potential of the human gut microbiome

The more we discover about the human gut microbiome and the gut-brain axis, the more questions arise concerning the influence that trillions of microorganisms have on the development of mental disorders and serious diseases such as cancer.

Indeed, in the not-so-distant future the gut microbiome will be integral to the development of novel therapeutics, probiotics and psychobiotics to treat gastro-intestinal disorders, improve cognitive functions, and prevent or treat mental disorders such as depression and schizophrenia, and conditions on the autism spectrum.

In a major review of this growing field of research, Prof. Leon Dicks, Distinguished Professor in Microbiology at Stellenbosch University (SU), states unequivocally that the full potential of the human gut microbiome, considered to be the second genome, has not yet been realised: “I am confident that we will be developing probiotics to treat dysbiosis (an imbalanced microbiome) and neuropsychiatric abnormalities,” he writes in the conclusion.

Prof. Dicks will receive his Doctor of Science-degree during SU’s March graduation ceremony this week. A Doctor of Science degree is awarded for published work of an exceptional standard, containing an original contribution to the advancement of knowledge and learning which has given the candidate international distinction in their field.

Prof. Dicks’ dissertation is a compilation of health benefits offered by Lactic Acid Bacteria (LAB) and summarises findings from his research published over the past 35 years. Since 1998 he has contributed to 264 scientific papers and 25 book chapters on lactic acid bacteria, antimicrobial peptides and probiotics.

In summary, he has found that gut microbiota has an immense impact on the gut-brain axis and overall mental health, specifically in terms of anti-inflammatory responses. For example, probiotics have already been shown to alleviate psychiatric symptoms stemming from inflammation in individuals with mental health conditions such as bipolar disorder, schizophrenia, obsessive compulsive disorder (OCD) and individuals on the autism spectrum.

However, he warns, “our understanding of exactly how gut microorganisms control cognitive behaviour, mood and neuropsychiatric disorders remain limited.”

Current thinking is that the ability of bacteria to communicate (by means of chemical signals, called ‘quorum sensing’), may play a role in communication between the gut microbiome and the brain. The nature of this “communication” is not direct, but involves an intricate control system of chemical signalling and immune response to keep the gut microbiome in a balanced state.

Prof. Dicks explains: “The modulation, development and renewal of neurons in the enteric nervous system (which is in close interaction with our digestive system) are controlled by gut microbiota. The gut microbiota produces short-chain fatty acids, which adhere to fatty acid receptors on the surface of the intestinal epithelial cells and thus interact with neurons or enter the circulatory system.

“Gut bacteria are not only sensitive to physiological variations in the gastro-intestinal tract, but also to the signal received from the central nervous system via the Vagus nerve (which runs from your brain to your large intestine) and the enteric nervous system. Minor activation of the Vagus nerve results in drastic changes in the production of neurotransmitters, which affects digestion, leaky gut syndrome, peristalsis, and immune regulation. Fibres of the Vagus nerve are not in direct contact with the gut or intestinal microbiota. Instead, signals reach the gut microbiota via 100 to 500 million neurons from the enteric nervous system in the submucosa and myenteric plexus (a network of nerve fibres in the muscular layers of digestive organs) of the gut wall.

“From all these studies, it is evident the intestinal barrier is controlled by fine-tuned communications between gut microbes and the host immune system. The complexity of those interactions raises the question about the level of our current understanding and eventually explains why is has been, up to now, difficult to develop specific therapeutic targets,” he writes.

Prof. Dicks has also done extensive research on the potential anticancer properties of bacteriocins. Almost all bacteria, human gut bacteria included, produce antimicrobial peptides to inhibit the growth of similar or closely related bacterial strains. In the same way, these peptides could be employed to inhibit the growth of cancerous cells. To date, however, despite several scientific reports and the patenting of three bacteriocins for their potential anti-cancer properties, we are still “a long way from understanding the efficacy of bacteriocins in anticancer therapy,” Prof. Dicks writes.

However, progress in metagenomics (the study of genetic material recovered directly from environmental samples), proteomics (large-scale study of proteins), heterologous gene expressions and nanotechnology, combined with the use of Artificial Intelligence software, may lead to the discovery and design of novel anticancer molecules. (With heterologous gene expression, scientists use competent cells to express and harvest specific genes that do not naturally occur in their hosts).

According to Prof. Alf Botha, head of the Department of Microbiology and Dicks’ study leader, the DSc-dissertation is a powerful synthesis of the best of our current understanding and knowledge of this important field: “It is a grand review with new and directional ideas and insights. It has again underlined the importance of this field, and will give direction to research across the medical, physiological and microbiological sciences.”

According to one of the external examiners, Prof. Dicks “managed to consolidate a number of very complex ideas regarding the gut microbiome and the gut-brain axis into a ‘coherent story’, and as a researcher in this field, this has been refreshing and enlightening, and has given me some food for thought!”

Prof. Dicks will receive his DSc-degree during Stellenbosch University ninth graduation ceremony on Thursday, 30 March 2023.