Insights from Probiota 2023
Probiotics paving their way into synergistic mental health treatment
This was the take home message from Richard Day, VP medical affairs & clinical development, ADM, during his presentation at Probiota in Barcelona earlier this month (February 8).
He explained why the firm considers this to be a particularly important area of research today.
“In recent years the conversation has changed around mental health. Twenty years ago, physical and mental health were seen and treated separately but now doctors and consumers really do see health unified between mental and physical.
Day noted that issues such as depression, anxiety, Parkinson's and migraines, are increasingly prevalent and the burden associated with these is significant.
What's more, drugs currently used are not reaching the route of the issues.
“Currently available management of these diagnoses is sub-optimal – therapy and drugs – talking therapies are difficult to access and drugs are often only met with partial success, so we have a huge need and only partially successful treatment available.
“The red thread that links all these diagnoses is a lack of treatments – they only look at reducing symptoms.”
In recent years there have been a vast number of papers published outlining a great number of physiologies and pathologies within the gut-brain axis, and subsequently consumer interest has also grown.
“I think it’s interesting that this scientific interest is converging with consumer interest. Popular press is publishing frequently about the gut-brain axis,” Day asserted.
Looking into the issue of depression, ADM scientists collaborated with researchers from the University of Oxford, to conduct a human clinical trial of 71 adults aged 18-50 with self-reported low mood or depression.
Individuals received a probiotic (Bio-Kult-protexin: 2 × 109 CFU/capsule) that contained 14 bacterial strains (Bacillus subtilis PXN 21, Bifidobacterium bifidum PXN 23, Bifidobacterium breve PXN 25, Bifidobacterium infantis PXN 27, Bifidobacterium longum PXN 30, Lactobacillus acidophilus PXN 35, Lactob. delbrueckii ssp. bulgaricus PXN 39, Lactob. casei PXN 37, Lactob. plantarum PXN 47, Lactob. rhamnosus PXN 54, Lactob. helveticus PXN 45, Lactob. salivarius PXN 57, Lactococcus lactis ssp. lactis PXN 63, and Streptococcus thermophilus PXN 66) or a placebo for four weeks. Mood, cognitive and emotional processing were all measured.
The resulting data revealed a clinically significant result in mood scores and they found the antidepressant effect was created via a different psychological mechanism to the one you would expect from a conventional anti-depressant.
Day explained that, put very simply, anti-depressants work by making “the bad things seem less bad and the good things feel better”.
However this can lead to the patient being susceptible to activities which provide highs such as gambling.
Whereas, with a probiotic “everything was brought more to the mid-line” so there wasn’t an increase in biased positive emotions, potentially making it a safer method of treatment.
The ADM team is also finishing a trial with the King’s College, London, in which they have taken 50 adults diagnosed with major depressive disorder being medicated on a conventional anti-depressant. They were randomised to receive either the probiotic cocktail or a placebo as well.
The paper is yet unpublished so Day wasn’t able to provide exact numbers but he said the results show a definite synergistic effect.
“I can tell you that the results we see here show a really strong synergistic effect. We see a much bigger standardised effect size compared to the Oxford trial. We can see that there is something happening between the antidepressant and the probiotic.”
Discussing anxiety, Day explained that a preclinical study in a zebrafish model of anxiety found that those given a two-strain probiotic (Lactobacillus rhamnosus CECT8361 and Bifidobacterium longum CECT7347) reduced anxiety within four months of treatment.
To translate this into human data, ADM is running a human clinical trial with 100 adults who self-identify as experiencing anxiety, who are not taking medication.
They will be given the two-strain combination probiotic or a placebo for 12 weeks and a number of health markers will be tracked. The team will then see if the heat-treated (postbiotic) version of the two strains has the same effects.
On the subject of Parkinson's Disease, Day explained that Alpha Synucleinography (α-Synuclein) is a presynaptic neuronal protein that is linked genetically and neuropathologically to Parkinson's disease (PD).
As a starting point for research, a nematode study revealed that fed bacillus subtilis PXN21 inhibits and reverses α-syn aggregation in a C. elegans.
As such, Day says ADM's scientists are hopeful that they will see similar results in their human clinical trial.
The dual centre study between the UK and Norway will recruit 50 adults diagnosed with PD, on a stable medication. They will receive the probiotic or a placebo and the researchers will look at the serum levels of the α-Synuclein levels, as well as microbiome changes.
Finally, explaining the research on migraines, Day revealed a recent randomised double-blind controlled trial of 40 episodic and 39 chronic migraine patients who received either the previously mentioned 14-strain probiotic or placebo to take alongside their usual treatment.
Duration and frequency of migraines was measured and resulting data revealed frequency of migraines reduced by around 40% in the probiotic group, with a 30% reduction in migraine severity.
“This was the first randomised placebo controlled clinical trial of its kind, using microbiome modulator in individuals with migraines,” noted Day.
"Here we may have an opportunity for patients with migraines to explore non-pharmacological management plan for their diagnosis."