Young woman smelling a bush of lavender, behind her a big lavender field.
Austrian researchers are combining olfactory training and microbiome research. First results show that specific daily smell training can help patients suffering from olfactory disorders. © Richárd Ecsedi/Unsplash

The corona crisis has placed a focus on the human sense of smell, because its loss can be one of the symptoms of the disease. Current studies suggest that in the course of the disease, damage occurs to cells of what is called the olfactory epithelium – tissue in the upper part of the nasal cavity specialised in detecting odours. When the tissue is restored after recovery, the sense of smell is usually regained as well. In exceptional cases, however, people may lose the perception of smells for an extended period or receive misleading sensory signals – an apple smelling like burnt rubber, for instance. Even if someone is not infected by the SARS-CoV-2 virus, there are many causes that can lead to the loss of the olfactory sense. The range extends from infections in the nasal area to inflammation, polyps and allergies, to head injuries and the decline of the sense of smell as a symptom of age. Interdisciplinary research teams at the Institute of Psychology at the University of Graz and at the Center for Microbiome Research at the Medical University of Graz are currently investigating whether specific daily smell training can help patients suffering from olfactory disorders, in particular younger patients. In the project “The Nose-Brain Axis”, they are also investigating the influence of microorganisms in the nasal cavity on the sense of smell. This includes the question of how changes in the ability to smell are reflected in brain activity.

Microorganisms impact human hosts in many different ways

“Millions of microorganisms dwell in and on our bodies: bacteria, fungi, viruses and archaea. They colonise our external and internal surfaces, such as our skin and mucous membranes. The microbiome influences our lives in many ways,” explains principal investigator Florian Fischmeister from the University of Graz, who collaborates with microbiome researcher Christine Moissl-Eichinger from the Medical University of Graz. “One of the things we want to find out is whether and in what way the nasal microbiome of a person suffering from anosmia – the inability to smell – differs from that of a healthy person. In contrast to the microbiome in the stomach and intestinal tract, there is still very little research on the nasal microbiota, and we want to do some catching up here,” Fischmeister adds. In a previous study, the researchers were able to show that hyposmic patients, i.e. individuals whose sense of smell is intact but performs less well than that of healthy people, presented a higher diversity of microorganisms on the olfactory epithelium. The analysis revealed that their microbiome included a species that produces butyric acid, which might have some bearing on the poorer olfactory performance. Another investigation also suggests that olfactory training, involving regular and conscious exposure to certain odours, could be a helpful strategy.

Smelling the roses every day

Based on these insights, Fischmeister and his colleagues are now working on a long-term study that combines olfactory training and microbiome research. “We invited test persons to complete a six-month training programme which involved smelling certain odours such as lemon or rose twice a day. They were also asked to intensively visualise and simultaneously think about this smell,” Fischmeister notes. At the start, at mid-point and at the end of the study, the researchers checked the test persons’ ability to smell and analysed their nasal and intestinal microbiome. In addition, they performed an MRI scan while the patients were being exposed to smells in order to analyse the correlation between the training and changes in the microbiome and developments in the brain. Data collection in the project has now been completed. 20 patients participated in the study and are being matched with a control group. “At this point we can already confirm that the olfactory training worked in our study. In some of the patients, the ability to smell improved significantly,” says the scientist. “The MRI imaging also shows that the networks in the brain associated with smelling are partially being restored.” Evaluation of the data collected in the study has been delayed owing to the corona crisis and is still ongoing. Should effects actually become apparent, this would bring research one step closer to a grand vision. “A long-term goal is to find key microorganisms whose presence may positively influence nasal function or which may at least work as biomarkers to suggest certain forms of therapy,” says Fischmeister. “Right now, however, we are still a long way from developing such a therapy.”


Personal details Florian Ph. S. Fischmeister's research focuses inter alia on the neuronal basis of chemosensory perception at the Institute of Psychology at University of Graz. He teaches at the University of Klagenfurt and the Sigmund Freud Privatuniversität in Linz. Previous stages in his career included the University of Vienna, the Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, and the Medical University of Vienna. The basic research project “The Nose-Brain Axis” (2017-2021) receives roughly EUR 386,000 in funding from the Austrian Science Fund FWF.


Publications

Parma, Valentina et al.: More than smell – COVID-19 is associated with severe impairment of smell, taste, and chemesthesis, in: Chemical Senses, 2020
Cecchetto, Cinzia; Fischmeister, Florian Ph. S.; Reichert, Johanna et al.: When to collect resting-state data: The influence of odor on post-task resting-state connectivity, in: NeuroImage, 2019
Bagga, Deepika; Aigner, Christoph; Reicher, Johanna et al.: Influence of 4-week multi strain probiotic administration on resting-state functional connectivity in healthy volunteers, in: European Journal of Nutrition, 2018
Kollndorfer, Kathrin; Fischmeister, Florian Ph. S.; Kowalczyk, Ksenia: Olfactory training induces changes in regional functional connectivity in patients with long-term smell loss, in: NeuroImage Clinical, 2015