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The Rise of Psychobiotics:

How and why these new probiotics are


conquering the world

Future impact, consumer reception and


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Contents

Introduction…………………………………………………………………………………3
The bugs and the brain – an intimate relationship……….……………………..…….4
Probiotics evolve into psychobiotics………………………………………..………….7
Stress and depression a mainstream concern…………………………...……….…..8
It’s all about the strain…….………………………………………………….…..……….9
The health claims game……………………………………………..…..……………….10
Online consumer engagement a viable route to building reputations ……….….11
Outlook…………………………………………………...……………………………..….14

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Introduction

Tiny organisms in the gut are controlling our brains. It’s the
stuff of science fiction. Except that it’s not fiction. Only
very recently have we become aware that the composition
of the gut microbiota has a profound impact on our mental
and neurological health. Research shows, for instance,
that the predominance of some species and/or the lack of
others appears to correlate to a significant number of
conditions like Parkinson’s and Alzheimer’s disease,
depression, anxiety, multiple sclerosis, schizophrenia and
attention deficit hyperactivity disorder (ADHD).1

This discovery has led to the premise that, by modulating


the microbiota in a targeted manner, we may be able to prevent and also treat these types of
conditions. The implications of this are, potentially, enormous. We are looking at a profound shift in
medical and pharmacological paradigms.

This new generation of probiotics is already busy carving out its niche. This paper assesses the future
impact of these “psychobiotics,” how they are received by consumers and what strategies brands may
adopt in positioning and promoting these products to their potential audience.

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The bugs and the brain – an intimate relationship

Keeping a human being operational and functioning is a monumentally complex task. To achieve this,
the body’s organs and systems need to work in concert with each other, connected by multidirectional
feedback loops. How these function in detail, what influences them, what happens when slip into a
state of imbalance and what might be done about it are continual topics for scientific investigation.

We now know that the central nervous system (consisting of the brain and the spinal cord) and the
gastrointestinal tract are engaged in a non-stop deep conversation with each other via both neural
and endocrine pathways. This interconnected system, which has been termed the Gut-Brain Axis
(GBA), has received a fair amount of attention in recent years.

One of the most intriguing aspects of this ongoing communication is that it’s not merely one organ
talking to another organ, but that the brain receives and transmits information to and from what,
technically, are “outsiders,” namely the microorganisms that make up the gut microbiome. For this
reason, when addressing the communication between the intestinal microbiota and the brain in
particular, researchers often employ the more specific term of “microbiome-gut-brain axis” or
“microbiota-gut-brain axis (MGBA)”2

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Tens of trillions of microorganisms reside in the human gut, outnumbering the body’s cells by at least
ten to one and contributing up to 2kg to our body weight. The number of different species of bacteria
is estimated at around 1,000, although, according to the European Society of Neurogastroenerology
& Motility, between 150 and 170 species tend to predominate in any given person’s gut. Around one
third of these are commonly found in virtually everyone, while two thirds are unique to the individual,
providing each and every one of us with our own specific microbiota “fingerprint.”

This microbial fingerprint has shown to be of relevance to neurological and psychiatric conditions. Our
understanding of how exactly the gut microbiota communicates with the brain and vice versa is still
in the early stages. It seems to do so via hormones, neurotransmitters and microbial metabolites, like
short chain fatty acids (SCFAs). There appear to be three main pathways of communication: the
endocrine pathway, the nervous pathway and the immune pathway.

Table 1 below shows a selection of conditions, which are associated with the prevalence or absence
of particular gut bacteria species and the metabolites they produce. Needless to say the scope of
neurological and psychiatric conditions affected by this interplay far exceeds this handful of examples.

Table 1: Selected conditions and their characteristic “fingerprint” of gut organisms & metabolites

Disease/Condition HIGH Prevalence Species & LOW Prevalence Species &


Metabolites Metabolites
Depression Bacteriodetes, Proteobacteria, Faecalibacterium, Bifidobacterium,
Actinobacteria, Enterobacteriaceae, Lactobacillus, serotonin,
Alistipes noradrenalin, short chain fatty acids
(SCFAs), kynurenic acid, kynurenine
Propionic, isobutyric and isovaleric
acids
Attention deficit Actinobacteria (Bifidobacterium Firmicutes (Clostridiales order)
hyperactivity genus)
disorder (ADHD)
Autism spectrum Streptococcus, Clostridiales, Firmicutes, Faecalibacterium,
disorder Comamonadaceae, Akkermansia, Ruminococcus, Proteobacteria,
Rhosococcus, Oscillospira, Desulvibrio, Fuscobacteria, Verrumicrobia,
Burkholderia, Collinsella, Bifidobacterium, Neisseria,
Corynebacterium, Dorea, Lactobacillus Alistipes, Bilophila, Dialister,
Parabacteroides, Veillonella
Acetic and propionic acid, p-cresol,
glutamate Butyric acid, tryptophan, kynurenic
acid
Alzheimer’s disease Blautia, Phascolarctobacterium, Ruminococcaceae,
Gemella, E. coli, Shigella, Ps. Turicibacteraceae,
Aueruginosa Peptostreptococcaceae,
Clostridiaceae, Mogibacteriaceae,
genera SMB53 (family
Clostridiaceae), Dialister,

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Clostridium, Turicibacter, cc115
(family Erysipelotrichaceae)
Multiple Sclerosis Akkermansia muciniphila, Parabacteroides distasonis
Acinetobacter calcoaceticus
Anorexia nervosa Methanobrevibacter smithii

Adapted from Skonieczna-Zydecka et al: Microbiome – The Missing Link in the Gut-Brain Axis: Focus
on its role in gastrointestinal and mental health, Journal of Clinical Medicine, 2018.1

The discovery of the bi-directional communication between the gut microbiota and the brain has
given rise to a new subgenre of medical & health literature. Image source: amazon.com

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Probiotics evolve into psychobiotics

The gut microbiota continuously evolves and changes from the moment we are born. It is subject to
multiple environmental influences, including diet, stress, various lifestyle factors, medication, climate,
interpersonal relationships, etc. An example of the latter is a mother passing her microbiota to the
infant through the intimate physical contact which characterises this relationship. With regards to
lifestyle, there are, for instance, marked differences in microbiota composition between urban and
rural dwellers, even in developed countries.2

Although firm causal relationships – does a microbial imbalance give rise to a pathology or is it the
other way around? – remain difficult to establish, it is not unreasonable to assume that modulating
the gut microbiome may have an impact on health outcomes.

There are numerous ways in which the microbiota may be modified therapeutically: through diet, the
administration of probiotics and prebiotics, and also by means of faecal microbiota transplants.

We are already witnessing the emergence of a novel class of drugs, termed “psychobiotics.” Coined in
2013, psychbiotics refers to “live organisms that, when ingested in adequate amounts, produce a
health benefit in patients suffering from psychiatric illness.”4 These novel probiotic drugs are said to
function by synthesising and delivering neuroactive substances, like serotonin and gamma-
aminobutyric acid (a SCFA), within the MGBA.

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Stress and depression: A mainstream concern

It has long been known that low levels of the neurotransmitter 5-hydroxytryptamine (aka serotonin)
in the brain are associated with mood disorders such as depression. There is, in fact, an entire class of
anti-depressant drugs based on this concept, namely selective serotonin reuptake inhibitors or SSRIs.
It was subsequently discovered that serotonin and serotonin receptors were far more ubiqutous in
the gut than in the brain, and intricately involved in the regulation of the GBA.5 A recent review
concluded that psychobiotics did indeed show promise as an alternative therapy in human mental,
neurodegenerative and neurodevelopmental disorders.6

Serious neurological and mental conditions such as Parkinson’s and schizophrenia aside, stress and
stress-related conditions are likely to affect virtually anyone, at least episodically, throughout the
course of their life, and some studies suggest that probiotics may be affective in combating this.7

GBA-targeted probiotics show promise in alleviating depression, and the potential audience for
psychobiotics in this area is huge. According to the WHO, depression affects more than 264 million
people of all ages globally.8 People are often reluctant to take drugs like SSRIs and monoamine oxidase
inhibitors (MAOIs), since they can have unpleasant side effects. Psychobiotics would be a much
preferable option for many, especially in cases of light depression.

Probiotic supplements have been on the market for decades and tend to be freely available to
consumers through health food shops, OTC from pharmacies and online. Some of these claim to
modulate the GBA, with mood enhancing and stress relieving among the most common positionings.

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It’s all about the strain

Research shows that probiotics are highly strain specific in their effects.9 A particular genus, e.g.
Bifidobacterium, harbours dozens (or several hundreds) of species (e.g. B. longum, B. animalis, B.
breve), numerous subspecies, and a potentially unlimited number of strains, since new strains can be
bred in the laboratory. An important consequence of this is that probiotic strains can be patented by
the company who creates them. Branded strains are already common in the probiotics market.

InnovixLab’s Mood Probiotic, for example, promoted as targeting the GBA to help cope with stress
and support positive mood and emotional wellness, employs Lactobacillus helveticus Rosell-52ND and
Bifidobacterium longum Rosell-175 in its formulation. InnovixLabs points out that these proprietary
strains, developed by Lallemand’s Rosell Institute for Microbiome and Probiotics in Canada, possess
clinically proven mood health properties, but, by contrast, have shown no efficacy when tested for
skin health and urinary tract infections.10

Image source

Bened Biomedical, a Taiwanese company, developed the trademarked Lactobacillus plantarum strain
PS128, which has shown some promising effects in children with autism spectrum disorder and
attention deficit hyperactivity disorder (ADHD).11 Last year, Neuraxpharm Group, a European
pharmaceutical company specialising in the treatment of central nervous system disorders,
announced that it had entereed into a collaboration with Bened Biomedical with the intention of
introducing PS128 into the European market.

10
Lactobacillus paracasei PS23 is another promising proprietary strain by Bened Biomedical and
currently on its way towards commercialisation. According to the company, it can boost brain
dopamine levels and ease anxiety.

The health claims game

As any industry observer knows, getting to the point of being able to make specific health claims on a
probiotic product is no easy feat. Some regulatory environments are more permissive than others in
this regard. The EU has, up to now, been among the most reticent. With the exception of a claim
pertaining to live yoghurt cultures improving lactose digestion, no health claims involving probiotic
bacteria have been authorised by the European Commission.

Other legislators aren’t quite so stringent. For example, in December 2019 we witnessed the approval
of two GBA-related health claims by the Brazilian Health Regulatory Agency (ANVISA) involving the
combination of Lallemand’s Lactobacillus helveticus Rosell-52 and Bifidobacterium longum Rosell-175,
which we mentioned earlier. Products marketed in Brazil containing a combination of these two
bacterial strains may therefore state that they

o “…may contribute to the reduction of feelings of anxiety in healthy individuals”

o “…contribute to the reduction of gastrointestinal complications such as abdominal pain and


nausea/vomit brought on by light to moderate stress in healthy individuals”

Back in 2016, Health Canada approved very similar claims for these two proprietary strains.

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Online consumer engagement a viable route to building reputation

Official health claims, however, are not the only route for probiotics to gain credibility with the
consumer, and this is encouraging news particularly for players operating in highly restictive
regulatory environments.

Mental and neurological conditions tend to have a drastically detrimental impact on one’s quality of
life and this motivates many sufferers (and/or their family members) to do their own research.
However, wading through and interpreting reams of turgid scientific papers is not within everyone’s
reach. Instead, today’s consumers increasingly put their faith in the judgement and experiences
shared by their peers. Such feedback is freely available through online product ratings and reviews.
From a brand strategy perspective, mining this type of data reveals a number of interesting insights.

Lumina Intelligence systematically analyses online consumer engagement with probiotic supplements.
Between December 2017 and January 2020, we looked at 1406 leading brands and 3111 band variants
from 1249 brand owners across 25 key markets globally. The level of online engagement is expressed
through the average star rating and the number of post-purchase reviews per product/brand/brand
owner, and the number of likes/followers on Facebook and Twitter.

As illustrated in Figure 2, after breaking down probiotic products by health positioning, gut-brain axis
positioned products received far fewer an average number of reviews than products with the
“classical” positionings leveraged by probiotics, such as gut flora, digestion, immunity and
constipation. The reason for this is that consumer awareness of the impact of the gut microbiota on
mental and neurological health via the GBA is still very low.

In terms of ratings, GBA positioned products fell just short of the average among probiotics, at 4.47
stars (out of 5) vs. 4.53 stars. For comparison, probiotics positioned as having bone health, eczema
and cholesterol benefits achieved a rating in excess of 4.6.

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Figure 1: Probiotics brands by health benefits (excludes digestion & immmunity), reviews and star
rating (global)

Source: Lumina Intelligence

Figure 2: GBA-positioned probiotics brands, by reviews and star rating (global)

On a brand level, Nutrimmun and Flora Udo’s Choice, a German and a US brand, respectively, came
out top in terms of consumer ratings. Source: Lumina Intelligence

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It deserves a mention at this point that quite a few probiotic products with a GBA positioning choose
to emphasise other types of ingredients present in their formulations, which are more closely
associated with mental/neurological benefits. This was also the case for Nutrimmun Probiotic Recur
and also in Garden of Life Dr. Formulated Mood + (refer to Figure 2 for consumer engagement with
these brands.)

“Contains vitamin B12, folic acid and a complex of bacterial cultures. Vitamin B12 contributes to the normal
functioning of the nervous system. Folic acid and B12 contribute to normal psychological function.” Image source.

Nutrimmun Probiotic Recur bases its claims around mental


stability and neurological functioning on the presence of folic
acid and vitamin B12 by drawing on relevant authorised health
claims. This is a common strategy employed by probiotic
products sold in the EU.

Garden of Life Mood +, on the market in the US, features the


adaptogenic herb ashwagandha and organic Alaskan
blueberries alongside probiotics to “support emotional health
and wellbeing.” In this case, the additional ingredients serve
product differentiation rather than presenting a roundabout
route to employing a health claim, as in the previous example.
Image Source

In a highly competitive environment, where consumers are increasingly basing their purchase
decisions on the feedback of previous customers, using the online space to foster consumer
engagement with their brands is absolutely key for probiotics players.

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Outlook

• The evolution of probiotics as GBA modulators is going to blurr the boundary between pharma
and the nutraceuticals industry even further. It is highly unlikely that probiotics’ use will ever
be restricted to the pharmaceuticals realm, since they seem to be largely free of side effects
and as such do not pose any risk to human health.

• The fact that condition-specific probiotic strains can be developed in the lab and subsequently
patented, creating a commercial incentive, is going to drive the development of psychobiotics.

• So far, most of our insights into the workings of the GBA and its targeted modulation for
therapeutic ends has been based on animal models. For the advancement of psychobiotics,
however, a solid foundation of well-executed human studies will be required. We expect the
research focus on this area to strengthen significantly in the future.

• Nootropics, also sometimes referred to as “smart drugs,” are substances said to promote
cognitive performance. This includes aspects such as mental focus, clarity, memory,
motivation, concentration, creativity, processing efficiency and reaction time. Caffeine is
probably the most widely used nootropic. Probiotics, on the other hand, are still significantly
underexploited in this regard. As the concept of the MGBA enters into mainstream
consciousness, we expect probiotics to gain traction as nootropics.

• Although official health claims will remain important in backing up GBA positioned probiotics
products, legislative environments are notoriously rigid and slow moving to when it comes to
taking into account new scientific insights. Consumer feedback on products, in the form of
reviews, rankings, social media mentions and direct responses to queries present another way
for brands to build their credibility and reputation. The importance of online engagement is
only going to grow.

• Personalisation is an important macro trend across virtually all of FMCG. This applies also to
diets - consumers are searching for foods and supplements, that are right for them and their
bodies. Microflora test kits are already available commercially. The use of such diagnostic
tools is going to spread, giving people greater insight into the composition of their own
microbiome. This will allow consumers to fine-tune their probiotics intake accordingly. As a
result, customisable probiotics offerings are expected to appear on the market, most likely
through the online channel.

Disclaimer: Lumina Intelligence has not verified the scientific validity of any of the claims promulgated by the
product examples cited in this paper. The information has been drawn from the details provided by the
manufacturer on product packaging and websites.

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References

1 Microbiome – the missing link in the gut-brain axis: focus on its role in gastrointestinal and mental
health. Journal of Clinical Medicine (2018) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306769/

2 Gut-Brain Psychology: Rethinking Psychology from the Microbiota-Gut-Brain Axis. Frontiers in


Integrative Neuroscience (2018) https://www.frontiersin.org/articles/10.3389/fnint.2018.00033/full

3 Gut Microbiota Info. European Society of Neurogastroenterology & Motility (2020)


https://www.gutmicrobiotaforhealth.com/en/about-gut-microbiota-info/

4 Psychobiotics: A Novel Class of Psychotropic. Biological Psychiatry (2013)


https://www.sciencedirect.com/science/article/abs/pii/S0006322313004083

5 Neurotransmitters: The critical modulators regulating the gut-brain axis. US National Library of
Medicine - National Institutes of Health (2018)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772764/

6 Psychobiotics in mental health, neurodegenerative and neurodevelopmental disorders. Journal of Food


and Drug Analysis (2019) https://www.sciencedirect.com/science/article/pii/S1021949819300158

7 Neuropsychiatric Disorders: Influence of Gut Microbe to Brain Signalling. Diseases (2018)


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163507/

8 Depression. World Health Organization (2020) https://www.who.int/news-room/fact-


sheets/detail/depression

9 Strain-Specificity and Disease-Specificity of Probiotic Efficacy: A Systematic Review and Meta-Analysis.


Frontiers in Medicine (2018) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949321/

10 Psychobiotics: probiotics for your mood. InnovixLabs (2020)


https://innovixlabs.com/blogs/insights/psychobiotics-probiotics-for-mood-health

11 Effects of Lactobacillus plantarum PS128 on Children with Autusm Spectrum Disorder in Taiwan: A
Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients (2019) https://www.mdpi.com/2072-
6643/11/4/820

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About the providers of this paper

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