Gut health: “You need to introduce a systemic change”

Gut health: “You need to introduce a systemic change”

Ali Kazemi, founder of nature-derived healthcare solution provider Metaceutic, tells HEQ about the holistic importance of gut health.

CEO Ali Kazemi, PhD, founded Copenhagen-based Metaceutic with the goal of addressing the world’s most prevalent lifestyle-related diseases and conditions at the root, identifying and rectifying the causes of issues affected by the gut microbiome. He speaks with HEQ about the surprising influence of the gut on mental and physical health, and tells us what Metaceutic is doing to help.

Do you feel that there is a lack of attention placed on natural resources when it comes to therapeutics? And is there a sense that many are seen as ‘holistic’ solutions with little efficacy?

There is this notion that natural resources are ineffective, yet the majority of pharmaceuticals currently on the market have their blueprint in natural compounds. Nature is already dominant in our pharmaceutical and therapeutic products – it’s just not getting the appreciation it deserves. The other issue pertains to drug listing: having spent more than a decade working for pharmaceutical companies in many roles, I think drug producers and pharmaceutical companies have spent too long focusing on treatment at the symptom level; and concentrating more on the phenotypic manifestation of a disease rather than its root causes. At the same time, we are observing an exponential global increase in lifestyle-related diseases which are oftentimes preventable and potentially reversible. Once we examine the deeper origins of these diseases, we find they are often rooted in either undernourishment or overexposure to certain compounds found in our food chain.

When we talk about holistic healthcare at Metaceutic, we are actually referring to the fact that we should examine human physiology and health with a broad lens, realising that we are living in symbiosis with trillions of bacteria which play an essential role in our wellbeing – this has not historically received a great deal of attention within medical care; and imbalances in the diversity of that ecosystem can actually trigger the onset of disease. In terms of determining the efficacy of holistic treatment, we need to go back a step and establish a solid definition of what constitutes efficacy itself: it has traditionally been determined within a narrow window, by identifying phenotypic changes in comparison to a control group. If the efficacy of a treatment is observed to be low by those parameters, it could of course mean that the treatment is not working, but it could also mean that the administration strategy – the dose, the control, or the timeframe of observations – may be biased. There are a lot of reasons why product testing may indicate low potential for efficacy.

Looking specifically at the gut microbiome, there have been multiple landmark studies in recent years suggesting that gut microbiota differ from person to person almost on a forensic level; it is unique and different even between close relatives. This means that if you want to treat or modify gut microbiota, you really have to address it on an individualised level. Efficacy testing therefore needs to take that uniqueness into account, otherwise it can skew the control results.

What can be done to change the perception of natural medicines and holistic treatments?

It is partly a cultural issue: some cultures around the world are much more receptive to alternative medicine and treatments derived from nature. The majority of diseases we are aware of today can be treated using some sort of natural compound; we should not view natural products as alien or ineffective, we have to realise that medical and health-enhancing treatments are being derived from natural resources. This is also why the pharmaceutical industry constantly seeks inspiration in nature before refining discovered molecules to targeted drugs.

Many of the benefits of plants and fruits and roots have evolved naturally: there is a reason why they have a certain type of chemical composition, often evolutionarily fine-tuned for protection from bacteria and parasites; there are a lot of natural pro- and antibacterial compounds in a lot of plants. As humans we host more bacterial species in our bodies then we have human cells; and we have 100 times more bacterial genes driving metabolic activities in our bodies than human genes. We are in very close symbiosis with our own internal bacterial populations; and it is not a long stretch to say natural products can actually make a difference for our physiology.

The importance of the microbiome in human health is being increasingly realised. How important is it with regard to improved cognition and mental wellbeing – the ‘psychobiotic gut’? How do your formulations take this into account?

The gut is an amazing organ; and I think that historically the medical field has not appreciated or studied it enough. Particularly in the pharmaceutical industry and therapeutics development, and particularly in the case of oral administrations as opposed to intravenous injections, there is a lot of focus on absorption into the upper GI tract, because we want the compounds to enter the bloodstream. This means that very little emphasis is put on what happens further downstream, in the lower GI tract and the colon; and this is where the bacteria are.

Humans are dependent on nutritional compounds derived from the food chain to meet our needs and keep us functioning. Multiple metabolically important compounds, vitamins and neurotransmitters – including serotonin – are all produced in the gut. Especially in the last decade, there have been a growing number of studies suggesting a link between the brain and the gut; so while we focus on the gut we took all of this research into account in developing our formulations. We also take into account the principles of evolutionary biology, which suggest that in order to change the biodiversity of an ecosystem – in this case, the gut microflora – you need to introduce a systemic change to the environment to push it towards the new equilibrium that you are seeking.

Our formulations are natural next-generation prebiotics that we develop using multivariate methods, to allow us to conduct multiparametric evaluations on how we combine plant-derived secondary metabolites: each individual compound may have a certain influence on a specific bacterial species, but it’s the combination of them that is key in our formulation development. We focus holistically on the gut microbiome and the hundreds of species that coexist there; and here is where we often see some sort of imbalance. Our formulations are developed in a way that allows us to shift that balance in a very targeted way.

Can you tell me a little about your product pathway, from formulation development to functional validation to personalisation?

We use a multiparametric system of design. Once a formulation has been designed, we have a screening platform where we evaluate formulations using in vitro gastrointestinal tract models and thereby simulate their impact on the gut microbiome, before integrating those results into a huge interconnected database, which covers the fingerprint, dose/range and efficacy results for each formulation. We undertake toxicology assessments of each formulation and compound, and then progress our key leads to human studies, using healthy volunteers. Using this workflow, we can develop hundreds of formulations, all of which have a unique gut microbiota fingerprint. Soon this process will allow us to meet our next key goal: the individualisation of treatment based on a customer’s gut analysis.

Your personalisation service is set to be launched soon. What will this entail? Will you also be offering additional information to clients, such as dietary or exercise advice?

We want to help our customers become more conscious of their gut health. Appetite regulation, mental stress, cognitive performance or dysfunction, and the immune system are all tied into the health of the gut. We believe in 2020 a person’s health status should not be hidden in some sort of journal; it should actually be on their phone or their watch or other personal devices, so users can have full awareness and be cautious about their own health at any time.

Our services include standalone products as well as analysis and supply on an individual level, but we will also place emphasis on encouraging a healthy lifestyle. We increased communication efforts in form of newsletters, blogs and podcasts aimed at educating our customers and raising awareness of the need for a healthy lifestyle. We also offer healthy gut diet plans where our dietitians develop dietary recipes, both to be made available for general use and more personalised recipes created as part of individual nutrition plans. We don’t think changing lifestyle can be done by taking some sort of a magic pill while sitting on your mobile phone: you need to be engaged in the process. That engagement often comes with awareness, so we want to emphasise transparency on health, combined with state-of-the-art analysis and bespoke product formulations.

In addition to the personalisation service, what else does the future hold for Metaceutic ApS?

We are looking into multiple collaborations with patient unions and clinics where we believe our products and services could potentially make a difference; and we’re looking to initiate a few clinical studies in the near future. Our vision is to offer an alternative treatment for people who are experiencing challenges such as weight management, stress and cognitive dysfunction – left untreated, all these issues can lead to severe chronic conditions requiring therapeutic treatments. I know how those therapies can offer life-changing solutions for patients in need, there’s no doubt about it, and I have been for a long time actively contributing to it; and yet I’ve always been driven personally by the idea of preventing the occurrence of these often lifestyle-related diseases. Metaceutic is moving into this direction; and we want to showcase the clinical evidence behind our products.

Metaceutic ApS
Ali Kazemi, PhD

This article is from issue 14 of Health Europa. Click here to get your free subscription today.

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