Immunity and infectious disease – the central role of the microbiome

The Human Microbiome Project has discovered that each microbiome contains up to 3.3 million unique protein-encoding genes.  This burgeoning area of research continues to highlight the importance of the microbiome and the extent of its reach.  One continuing area of study is looking at its relationship to our immunity. It is now understood that a balanced microbiome is central to the proper development and functioning of the immune system, which helps to explain why 80% of immunity is found within the gut.  In 2018, researchers Libertucci and Young posited a new function of the microbiota: the ability to influence susceptibility to and outcomes of infectious diseases.

It does this by preventing the growth, persistence and subsequent infection by non-native microorganisms, known as colonisation resistance   Our indigenous microbiota directly inhibits any pathogens using protective mechanisms contained within itself, and indirectly helps by signalling host immune defences.  

The role of the gut mucosal system

The gut mucosal immune system plays a central role in this. Its defences include a single layer of tightly packed gut epithelium cells covered in a thick mucus layer, secreted antimicrobial peptides (AMPs), and the dynamic and adaptive production of targeted immunoglobulins in response to pathogenic challenges. What is now known is that the bacterial composition of our microbiome directly impacts all these. 

The tight junction proteins that maintain the epithelial barrier can become impaired in the presence of certain bacteria, such as C. difficile and Yersinia enterocolitica.  Mucin, the major component of our mucus layer, increases with certain commensals, such as E coli, but degrades in the presence of others, such as C difficile.  AMPs are upregulated by certain commensals, such as Bacteroides thetaiotaomicron and Bifidobacterium breve, and also in the presence of short chain fatty acids (SCFAs).  AMPs are part of our innate immunity, protecting our epithelium by binding and disrupting the membranes of bacterial pathogens as well as by inhibiting viral replication, and are secreted at all mucosal surfaces.  Our other innate immune defence, secretory IgA, is also dependent on an intact microbiome, and can increase production in the presence of certain commensal bacteria, such as Lactobacillus reuteri.   

Targeted adaptive defence production

Our targeted adaptive defence against pathogens is through the production of antibody producing cells (APCs).  These T and B-lymphocytes proliferate in an area called the Peyer’s patches, found in the ileum of the small intestine.  Again, commensal intestinal microorganisms are essential in both the maturation of these secondary lymphoid organs and in alerting them when they need to pay attention to an incoming threat.

This means that any disruptions in the established microbiome can result in an altered immunity and increased infection susceptibility.  For example, antibiotic administration can diminish large portions of the microbiome and predispose individuals to C. difficile infection.   An impaired barrier function can allow the release into the bloodstream of lipopolysaccharides (LPS), the structural component of gram-negative bacterial cell membranes which are shed when the cells die, and this can constantly activate our immune systems and lead to the chronic low grade inflammation seen in many conditions.

With regards to viruses, the interactions between them and the commensal microbiota are not so clear. We know that healthy individuals harbour viral communities that are not pathogenic, called the human virome.  These resident viruses use evasion mechanisms to enable immune system tolerance (which are also, unfortunately, used by pathogenic viruses) and can also modulate immune responses.

Protective role of bacteria

Some bacteria have been shown to be protective against certain viral pathogens.  The Lactobacillus genus inhibits murine norovirus and   Bifidobacterium breve inhibits rotavirus.  The gut microbiota can also mount distal antiviral protective mechanisms, such as in the lung.  Gut probiotics such as Lactobacillus paracasei and plantarum have been shown to influence inflammatory responses there during influenza virus infections.  This is a fairly new field of research, which will no doubt accelerate with the emergence of COVID-19.

Optimising microbial defences

So, to optimise our microbiome function in order to protect us in the event of an infectious disease, there are a number of things we can all do.  Minimising alcohol consumption, giving up smoking and managing stress will all have a really positive effect.  And in terms of diet, the research indicates that we need to expand our dietary diversity of whole plant foods and reduce saturated fat intake. 

And there are also some promising interventional targets we can use, such as: modulating the microbiome using targeted probiotics, prebiotics and polyphenols; boosting secretory IgA levels and increasing mucin production. 

Using probiotics, prebiotics and polyphenols.

Some probiotics have been shown to improve barrier function.  One double blind, placebo-controlled study using MegaSporeBiotic, showed that 30 days of supplementation could reduce endotoxemia from a leaky gut after a high fat meal by 45%, as well as significantly reduce many other inflammatory cytokines.  (McFarlin et al., 2017)  Many probiotics struggle to survive the harsh gastric passage, but spores can and do, entering the intestines completely viable, to have a more prolonged and persistent effect.  This research suggests that the spores were able to strengthen the integrity of the intestinal lining to keep endotoxins out of the bloodstream.

Another way to beneficially modify the microbiome is to target the growth of keystone species, such as Akkermansia municiphilia and  Faecalibacterium prausnitzii, as well as Bifidobacteria, with carefully selected prebiotics made up of researched non-digestible oligosaccharides, such as kiwifruits. Keystone species have been shown help maintain a healthier microbiome balance, and also improve tight junction function. 

Other research has highlighted the importance of polyphenols (PPs) and their metabolites in the modulation of the microbiome and in barrier function through antimicrobial, antioxidant, anti-inflammatory and anti-proliferative functions, at both an intestinal and systemic level.  They can both improve microbiota composition as well as counteract pro-oxidant and/or pro-inflammatory responses.

Protecting the gut mucosal system

Increasing secretory immunoglobulins, which bind and neutralise toxins in the lumen and mucosa before they even reach the intestinal epithelium, can also be effective.  Nutrients that have been shown to have a positive effect on its production and secretion include essential omega fatty acids, glutathione, glycine, phosphatidylcholine, vitamin C, zinc and colostrum.

Another approach is to increase mucin production to shore up the mucus layer lining the gut endothelium.  Nutrients that have been shown to do this include the amino acids L-threonine, L-serine, L-proline, and L-cysteine, where in one study on rats, their supplementation increased production by 95%.

In conclusion

In conclusion, it is clear that our microbiome plays a central role in how each of us will respond to an infectious disease and that there are steps, as outlined above, that we can take to enhance it our immune function. What is now clear, is that the two are intricately connected.

Karen Jones is a practising BANT Registered Nutritional Therapist who offers education and practitioner support to Microbiome Labs UK. After graduating from CNM, she studied the microbiome extensively under the guidance of Adam Greer.  She can be contacted via karen@tmcventures.com. 

For more information on Microbiome Labs products and their Total Gut Reset Programme, or their support programmes for practitioners, please visit www.microbiomelabs.co.uk. Microbiome Lab’s products are available exclusively to qualified healthcare practitioners and their clients.

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