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Immunity

An important function of the gastrointestinal (GI) tract is its role in our immune health.  In fact, the gut is the largest immune organ of the body; over half of all immunologically active cells in the body are located in the intestines.

 

Each time we eat or drink, food antigens and microbes are introduced into our body and the immune system must be able to detect and respond accordingly to them.  Specifically, we need to tolerate food antigens and harmless microbes, whilst at the same time detect and destroy microbes that have the potential to cause harm. 

In addition, we also have a vast community of microbes, called the commensal gut microbiota, living inside us that again we need to be able to tolerate. 

The Gut-Associated Lymphoid Tissue

Similarly to other mucous membranes throughout the body, the gut has a mucosal immune system, aptly known as the ‘gut-associated lymphoid tissue’ (GALT).  

Sitting beneath the mucous layer is the intestinal mucosa, which comprises; a single layer of epithelial cells, the lamina propria, and muscularis mucosae, which together separate the gut lumen from the circulatory system.1 

Immune cells are found throughout this structure, but particularly concentrated in lymphoid follicles called Peyer’s patches.  M cells are responsible for transporting luminal antigens to the underlying immune cells, where subsequently either an immune response is triggered, or they are tolerated.2 

 

1. Peled et al. (2016) Blood 128(2): 2395-2402

2. Jung et al. (2010) Int J Inflam. 2010:823710

Gut Microbiota & Immune Health

The ‘Hygiene Hypothesis’ has been suggested as a driving factor for the increase in immune related conditions in Western countries.  This suggests that children who are raised in an overly clean environment are not having adequate exposure to microbes and that might disrupt the development of the immune system.

Similarly, germ free-mice, those who have been born and raised in a sterile environment and subsequently do not have a gut microbiota, do not have a properly developed GALT.  Specifically, they have fewer and smaller Peyer’s patches.  These mice have a weaker immune system, so when exposed to pathogens are more susceptible to infections.1

 

1. Round & Mazmanian (2009) Nat Rev Immunol 9(5):313-323  

 

Here we take a look at the research investigating the role the gut microbiota has in specific immune related conditions....

The Gut Microbiota & Allergies

Atopic disease describes a triad of conditions, including; eczema (atopic dermatitis), asthma and hay fever (allergic rhinitis), which often present together.

Although there is a genetic contribution to atopic disease, it is suggested that this alone cannot account for the rapid rise in incidence of the disease in recent times.  

More than 150 million Europeans suffer from chronic allergic diseases and the current prediction is that by 2025 half of the entire EU population will be affected’ Allergy UK

 

The gut microbiota has been suggested as having a role.  When the gut microbiota of those with atopic disease is compared to those without, there are differences observed.  Particularly during early life, those with atopic disease have been shown to have reduced bacterial diversity with lower relative abundance of bacteria belonging to the genus Bifidobacteriaceae and Lactobacillaceae and greater abundance of Bacteroidaceae, Clostridiaceae, and Enterobacteriaceae.1 

 

There are a number of factors that can influence gut microbiota diversity, particularly during early life which have been associated with atopic disease, including:

 

MODE OF DELIVERY

Infants who have been delivered by caesarean section (c-section) have an increased risk of developing asthma (OR=1.22, 95% CI=1.14-1.29).5

Infants are generally considered to be sterile when in the womb, and our mode of delivery has important consequences on the initial microbes that colonise the infants’ gut.  Infants delivered vaginally will have a normal ‘seeding’, that closely resembles the mothers vaginal and faecal microbiota6, whereas those born by c-section are more commonly dominated by microbes that are associated with the skin microbiota6, and are often lower in diversity7.

 

METHOD OF FEEDING

Infants who have been exclusively breastfed during their first three-months of life have a reduced risk of developing atopic dermatitis, especially when there is a familial history of atopy (OR=0.68, 95% CI=0.52-0.88).3

Formula feeds provide adequate nutrients for infant development, however they lack the microbes and human-milk oligosaccharides (HMOs) which are present in breast milk. HMO’s have been shown to have a prebiotic effect.  They are only partially digested in the small intestine, so when they reach the colon they are fermented by Bifidobacteria resulting in the proliferation of a Bifidobacterium-rich infant microbiota.4  

 

PACIFIER CLEANING METHOD

Infants whose pacifier is cleaned by their parent sucking it, as opposed to other cleaning methods such as hand washing or sterilising, are less likely to have asthma (OR=0.12, 95% CI=0.01-0.99) or eczema (OR=0.37, 95% CI=0.15-0.91).  This method of cleaning also resulted in changes to the infant’s salivary microbiota.2

 

 

 

1. Zimmermann et al. (2019) J Allergy Clin Immunol 143(2): 467-485

2. Hesselmar et al. (2013) Pediatrics 131(6): e1829-37  

3. Gdalevich et al. (2001) J Am Acad Dermatol 45(4): 520-7

4. Marcobal et al. (2010) J Agric Food Chem 58(9): 5334-5340

5. Thavagnanam et al. (2008) Clin Exp Allergy 38(4): 629-633

6. Dominguez-Bello et al. (2010) PNAS 107: 11971-5

7. Azad et al. (2013) CMAJ 185: 385-394