The Microbiome And Immunity: Understanding Your Body's First Line Of Defence

The microbiome that a human body accommodates is genetically diverse and has more genes than the human genome itself.¹ Therefore, it should not be surprising that the unique microbial community you possess influences bodily functions, including immunity.

The human microbiome plays a crucial role in the development of immune system components.² Microbiota associated with the body's natural barriers regulate immunity, directly and indirectly. Microbial metabolites train the immune system to recognise and respond appropriately to any foreign body.^3,4

In this article, you will understand the interplay between microbiota and the immune system and its effect on health.

Understanding the partners: An intimate relationship between the microbiome and the immune system

Human microbiome: From harmless companions to beneficial partners

Microorganisms began colonising your body from the moment you were born. While many permanently established themselves in/on various regions of your body, others may have resided for a defined period and left after.  

Various factors influence the distribution and diversity of the microbial community: your age, diet, health status, stress, geography, medical history, and lifestyle.⁵  

The microbial residents can range from harmless companions (commensals) that neither harm nor benefit the host (you) to beneficial partners (mutualists), where both the microbes and you benefit from the intimate relationship.

Learn how your food choices shape your microbiome and how stress affects your microbiome.

The immune system: A complex network of specific and non-specific defences

Immunity is the ability of our body to protect itself from diseases by fighting against pathogenic microbes and other agents.

The immune system that helps with immunity consists of innate immunity, which acts as the first responder against any invading foreign body, and adaptive immunity, which provides a targeted and stronger response to specific pathogens.

Innate immunity is a non-specific defence, i.e., the rapid responders do not specifically recognise foreign agents, including potentially harmful microbes, when acting upon them.⁵ More like a shoot-on-sight approach. 

Unlike innate immunity, the response of adaptive immunity is slow and specific to an invading microbe. However, the response upon a second encounter is rapid and stronger due to a memory response.⁵

Table 1. An Overview of the Immune system⁵

Your body’s first line of defence: A well-coordinated operation

The physical and chemical barriers work together to combat invaders under the influence of mechanical forces (e.g., tears, expulsion of mucus). 

Microbiome and physical barriers: A combined defence strategy

How does the skin barrier collaborate with the microbiota to protect you?

The physical barriers shield the underlying tissues susceptible to invasion (infection). Skin is the largest barrier and serves as your first line of defence. The multi-layered keratinised epithelium strengthens the skin.⁶ 

Stationed at this line of defence are diverse microorganisms (bacteria, fungi, and viruses) determined by the skin’s microenvironment (pH, moisture, oil, and salt content) and other factors, including your diet.⁶ 

The impermeable skin barricades any attempts by pathogenic microorganisms to invade. The microbiota contributes to maintaining the integrity of the skin barrier. Microbial metabolites promote epithelial differentiation and replenish skin components, driving skin repair and preventing dehydration.⁶

The skin and its microbiota secrete lipids and acids that fortify the barrier. Further, the microbiota breaks down the lipids to produce fatty acids. The fatty acids have multiple effects:^6,7,8

• Dissuades pathogenic microbes from invading
• Maintains an acidic skin surface, hostile to encroaching pathogenic bacteria 
• Stimulates the antimicrobial secretions by the skin components

The antimicrobials synthesised by your innate immune system, along with the microbiota's antimicrobials, strengthen the defence against the pathogenic invaders.⁷ 

How your mucous membrane and microbiome support healthy immunity

The mucous membrane lines our nose, mouth, lungs, urinary tract, and gastrointestinal (GI) tract. The epithelial cells of the mucous membranes produce the slimy mucus that lubricates and protects the cells.⁹

In the GI tract, the mucus coating the epithelial cells protects them from chemical, mechanical, and external threats, including pathogens and toxins. Thereby earning the title of mucus barrier—the first line of protection of the GI tract.⁹ 

By now, you should know that microorganisms reside in your GI tract too. The mucus-coated epithelial cells line the tube-like intestine's lumen (hollow part). A diverse and balanced gut microbiota thrives in the lumen near the mucus.

The nutrients and attachment sites of the mucus layer condition the colonisation of the microbiota. In return, resident bacteria produce metabolites that stimulate mucus secretion to form and maintain the integrity of the mucus barrier.⁹

Additionally, the antimicrobials produced by the resident bacteria directly inhibit the colonisation of harmful microorganisms for space and nutrients. 

Autonomous defence: How the microbiome acts as the first barrier to invading microbes

The microbiome is an important first line of defence. The established resident microbiome prevents infection by fiercely competing for space and nutrients. The microbiomes produce antimicrobials, including antibiotics, to inhibit invasion by directly killing them.^6,7,8 

In instances of invasion, the population of the pathogenic microorganism is controlled by cutting off quorum sensing, the microbial communication system, through enzymes. Thereby preventing colonisation of the pathogenic microbes.⁶ 

Research has indicated the ability of the microbiome to reduce the pathogenicity of the invading pathogen by disrupting their communication (quorum sensing).⁷  

Microbiome metabolites: A collaboration beyond the intestinal lumen

Today, there is concrete evidence that the gut microbiota regulates immune responses outside the gut, in addition to its local effect.¹⁰ Though the gut microbiota is stationed in the intestinal lumen and segregated from the immune cells through the mucus barrier, cross-talk between the microbiota and the immune system occurs.¹¹

The microbial metabolites from protein and carbohydrate metabolism coordinate between the microbiota and the immune system. For example, the metabolism of dietary fibres produces short-chain fatty acids (SCFAs) like propionate, butyrate, and acetate.^10,11 

While the microbiota resides in the gut, its metabolites can move across the intestinal barrier.¹⁰ The metabolites, including SCFAs, circulate to various parts of the body and stimulate:^3,4,6,10

• Immune response in distant tissues

SCFAs bind to specific receptors on immune cells and elicit a suitable response, including reducing inflammation, suppressing excessive immune responses, recruiting immune cells, and killing overactive or damaged immune cells. 

• Adaptive immunity

The microbial metabolites modulate innate immunity and activate adaptive immunity, triggering antibody production.

In the gut, the metabolites such as butyrate (SCFA) promote:^10,11

• Increase in intestinal barrier integrity
• Decrease in gut inflammation
• Decrease in microbial (resident and pathogen) translocation across the barrier
• Anaerobic condition conducive for the microbiota producing SCFA

FAQs

Can my immune system recognise the resident microbiome to spare it and not the pathogens?

Your immune system can recognise and differentiate between friendly microbes (resident microbiome) and pathogens. An immune response is triggered when a microbe damages tissue or invades barriers. Unlike pathogens, your microbiome remains compartmentalised. 

Also, the immune system monitors microbial structures, metabolites, and biological roles.^4,12 Meanwhile, your microbiome makes its beneficial roles evident. The immune system targets harmful pathogens while sparing your microscopic partners, recognising their contributions.

How do alcohol consumption and smoking destroy my first line of defence?

Your microbiome stays within specific areas of the body because of natural barriers. The mucous membrane is a barrier in the lungs and the intestines. This barrier produces mucus and antimicrobials that shape the microbiome. 

Smoking can disrupt the barrier in the lungs, while alcohol consumption disrupts the intestinal barrier. The damaged barrier loses its function of protecting from pathogens and maintaining a balanced microbiome. Translocation of the microbes across the damaged barrier could trigger a non-specific immune response, leading to systemic infections, sepsis, and multiple organ failure. 

Can antibiotics cause breakouts?

Your gut and skin are connected (gut-skin axis).⁶ Poor diet, stress, or antibiotic use can affect the gut microbiota. An imbalance in the gut microbiota can trigger skin inflammation due to the affected production of SCFAs that execute anti-inflammatory activities. 

Additionally, a disrupted gut microbiota can alter the physical, chemical, and microbial composition of the skin barrier.⁶ This makes the skin susceptible to infections, dryness, and inflammation.  

Learn how to naturally nourish your microbiome to support gut health and maintain a balanced gut microbiome after an antibiotic course.

Summary

• The first line of defence is a rapid and non-specific response by physical and chemical barriers
• The skin and mucous membrane are the physical barriers that ward off foreign agents in association with the microbiome
• The microbiome boosts the first line of defence (innate immunity) directly and indirectly
• Microbial metabolites with antimicrobial and quorum-quenching properties directly eliminate the competing pathogen
• Indirectly, the microbial metabolites trigger innate and adaptive immune responses
• Microbial metabolites enhance the synthesis of antimicrobials and mucus by the physical barriers