Inflammation is the price we pay to have a functioning Immune System
For most of human evolution, the biggest killers have been foreign invaders in the form of microbial pathogens. But the gears have shifted. Medical and public-health advances have so vastly reduced the death toll from microbes that today’s leading killers spring from within. People are living long enough to acquire devastating bug-free disorders such as heart disease, strokes, cancer, osteoarthritis, Type 2 diabetes, autoimmunity and neurodegenerative syndromes such as Alzheimer’s.
A common element in all of those appears to be inflammation — not the intense, temporary, acute variety that’s actually helpful when you run a fever while you’re fighting off an infection, but another kind that’s stealthy, steady and destructive, resulting in our immune system to go haywire. It becomes less capable of protecting us against infections and cancer or responding to vaccinations but, paradoxically, increasingly prone to wallowing in a state of vague, nonspecific irritation that’s called chronic low-grade inflammation. Along with this accumulation of chronic low-grade inflammation, comes an increasing vulnerability to disease.
"All disease begins in the gut" Hippocrates
Research in the past decade has highlighted the importance of the gut to our overall wellness and health. Gut health covers multiple positive aspects of the gastrointestinal (GI) tract, such as the effective digestion and absorption of food, the absence of GI illness, normal and stable intestinal microbiota, effective immune status and a state of well-being. There is a delicate interaction between the host and the microbiota, and the disruption of this balance can compromise the homeostasis and survival of the entire organism, affecting human health, disease, and aging, even in organs distant from the gut.
Gut health maintenance involves continuous interaction between two key functional elements, the Gut Microbiota and the Mucosal Immune System. The process of sampling and communication between those two elements is the key to understanding the complex mechanisms that maintain gut health
The Gut Microbiota
67% of the body's total cell count is of microbial origin
The gut microbiota, consisting of the trillions of microorganisms contributes to energy homeostasis, prevents mucosal infections and mitigates immune system hypersensitivity. Most important, it contributes to the maintenance of an intact GI barrier that is closely related to infectious, inflammatory and allergic diseases. Any impairment of the GI microbiota, for example, by administration of oral antibiotics or lifestyle choices, affects the functionality of the host’s local defence systems. At the same time, any malfunction of the epithelium or the mucosal immune cells affects the microbiota composition, diversity and functionality. Especially, the GI barrier, and consequently gut health, are directly altered not only by local disturbances but also by any systemic burden. A normal GI microbiota of rich diversity, and more importantly an intact mucosal immune function that counteracts and cooperates with the existing microbiota, are thus needed to maintain gut health.
The Mucosal Immune System
The gut hosts >70% of our immune system's cells
The gut mucosal immune system both controls the gut microbiota and depends on it, as the continuous challenge of microbial antigens to the mucosal immune system is required for its normal development and function. To this end, it is not surprising that the mucosal immune system contains cells capable of recognising microbial antigens by specific receptors that form the basis of the communication between those two elements. This way any danger from pathogens can be quickly recognised and dealt with, while at the same time the friendly coexistence of microorganisms and host in the gut is maintained.
Under normal conditions, those mechanisms allow regulation of inflammatory responses to harmless antigens, such as food antigens or microbial antigens derived from friendly commensals, to achieve and maintain mucosal tolerance.
Host protection and maintenance of gut health is dependent on the ability of the mucosal immune system to regulate the complex balance between the defence against and the acceptance of the gut microbiota, without the generation of additional inflammation.
From gut microbiota to therapeutics via AI and synthetic biology
At veMico, we have been exploring a new avenue to prevent inflammation built up through a class of gut commensal derived molecules that interact with innate immune cells and increase thus the ability of the mucosal immune system to tolerate gut derived inflammatory signals, without the need to initiate a systemic inflammatory response.
Innate immune cells are directed by pattern recognition receptors (PRRs) located on their cell surface, in the cytosol, and within endosomes.
The interaction of innate immune cell receptors with chemical structures is the “molecular language” through which the body determines self from non-self. Understanding and manipulating these structures holds the promise of creating better vaccines, modulating the inflammatory response to disease, and better understanding how molecular structure influences the immune response.