As we control infectious diseases, there is increasing incidence of immune-mediated disorders, such as Crohn’s disease, multiple sclerosis and type one diabetes, which are autoimmune conditions, as well as asthma. We have also seen an exponential increase in the incidence of autism in the US. This observational shift from infection to immune-mediated conditions is a major changing paradigm that is necessary.  

In spite of considerable progress in medicine, chronic diseases have been rising in incidence, uncontrolled for over 60 years. 

What we have been able to observe when we look at the microbiota is the common thread in chronic conditions is dysbiosis. That relates to the central nervous system, the gastrointestinal arena, metabolism, and an overall immunity. We could also observe is in many instances leaky gut syndrome, an inflammatory state, and oxidative stress come with these situations. Beyond this was a combined alteration of microbiota and host parameters. Faecal microbiota transfer is geared to alleviate symptoms and in some cases it’s been considered as one way to document causality. 

Inflammation is driven by both microbiota and leaky gut syndrome. Inflammation drives oxidative stress and possibly oxidative stress will aggravate alteration of the gut microbiota. These causalities are typical of a symbiosis.  

Low gene count is a health stratifier, associated with altered metabolic and inflammatory traits in obesity, non-response to calorie restriction in obesity, severity or progression in acute liver conditions, and non-response to cancer immunotherapies. Intestinal microbiota richness is associated with a better response to anti PD-1 immuno therapy, for example.  

So, when we look at the vicious circle, we have tools that we can use to assess the microbiota, to assess intestinal permeability, to assess inflammation and oxidative stress. We have biomarkers that are available that would allow us to take a more global look at the symbiosis rather than just looking at certain parameters. And that could potentially lead us to the situation where the clinician could prescribe microbiota assessment.  

Bioactives can be used to tackle the system in a more holistic and global way. This is what I propose as a new paradigm. For example, we used a mouse model of depression. What was found was three bioactives combined do as well as an antidepressant. There was a synergistic efficacy comparable to tricyclic parenteral clomipramin. One of the bioactives was a probiotic. 

TAKE-HOME MESSAGES 

Circular causalities and alternative stable states may apply to host-microbes symbiosis. Altered host- microbes symbiosis leads to loss of protective functions. 

Monitoring includes integrating microbiota and host parameters.  

Prevention or cure is targeting several triggers of a vicious circle in altered host microbes symbiosis, with a crucial place for my for bio active in combination. 

Innovation in trial design includes novel methodologies are needed to tackle clinical conditions involving alteration of host microbes symbiosis.  

The next frontier in personalised nutrition and clinical practice is prescription and delivery of host microbes symbiosis profiles.