The Gut and the Immune System

The Gut and the Immune System

By Dr. Patrick Lovegrove Medically Reviewed by Lindsay Langley, BSN, RN, CHT

Posted Tuesday, October 12th, 2021

Every day we seem to be learning more and more about the relationship between gut microbiota and immune health. Meanwhile, researchers discovered that the immune system doesn’t activate during nine weeks into gestation. In short, the intestinal epithelial cells work to eradicate damaged cells long before our organs develop. (See “Innate Immunity and the Microbiota” below.)

The microbiota and the immune system work closely together to protect the body from disease; it also produces vitamins and creates new healthy tissues. Keeping them in balance is delicate and must begin with selecting healthy lifestyle choices. And these 5 things you didn’t know that hurt your microbiome.

In this article, we’ll explore the connections between gut microbes and the immune system, how to help them remain in balance, and what it means to get rid of harmful bacteria. 

Gut Microbiota and Immune System Homeostasis

Gut microbes function symbiotically with the immune system, providing balance and health. Alterations in the population of microbes in the gut can lead to immune dysregulation. We now know the critical role of gut microbes and how they have evolved over millennia. The immune system’s role is to quickly eliminate pathogens and toxins, more importantly, create new healthy tissue. Patients with autoimmune conditions suffer as their immune system falsely identifies healthy tissue as a foreign body. 

We can now analyze how the gut microbiota and immune system interact thanks to advanced sequencing techniques. Using either germ-free mice or manipulating the gut microbiome has allowed researchers to discover that the microbiota shapes the innate and adaptive immune response. The gut microbiota doesn’t just shape the local intestinal immune system. It also impacts systemic immune responses to achieve homeostasis. 

Innate Immunity and the Microbiota

Several interconnected systems work together to provide immunity by removing pathogens and toxins from the body—notably, a tolerance to our bodily tissues and keeping beneficial bacteria intact to ward off autoimmune conditions. The cells involved in the innate immune system have co-evolved with the microbiota, as detailed below. The microbiota regulates the essential cells that protect us from diseases. 

There are five groups of cells involved in the innate immune system:

• Antigen-presenting cells (APCs) – A group of immune cells that present antigens to T cells and lymphocytes. The gut microbiota regulates the development of APCs. 
• Neutrophils – Recruiting microbiota to regulate neutrophils, which comprise 40-60% of white blood cells. 
• Natural killer (NK) cells – Secrete cytokines and act on other cells, such as macrophages, to mount an immune response. There is much crosstalk between NK cells and the microbiota as they work together to promote health and ward off disease. 
• Mast cells (MC) – mastocytes or labrocytes containing histamine and heparin: are part of the immune and neuroimmune systems. MCs act at the intersections between intestinal mucosa, microbiota, and the nervous system. 
• Intestinal epithelium – This single-cell layer plays an essential role in the immune system from conception, forming a physical and chemical barrier to protect intestinal mucosa while working symbiotically with the microbiota to remove damaged cells quickly. 

Note that Gamma delta (γδ) T cells are considered to be the bridge between the innate and adaptive immune systems. Finding microbiota plays a crucial role in maintaining the function of γδ T cells.

Adaptive Immunity and the Microbiota

The gut microbiota plays a vital role in developing white blood cells, such as T cells. The microbes Clostridia, a class of Firmicutes, are capable of promoting the induction of human regulatory T cells (Tregs). The two fundamental types of cells involved in the adaptive immune system are:

• T cells (4 major groups) – T cells play a vital role in the adaptive immune system. Th17 offers protection against parasites. Th2 regulates the immune response, Th1 protects against intracellular microbes, and Treg governs the immune response.
• B cells – Most are immunoglobulin A (IgA) secreting plasma cells, a type of antibody that plays a critical role in the immune function of mucous membranes. The microbiota is a significant driver of Iga production. 

Getting Rid of Bad Gut Bacteria (Hint: It Isn’t What You’d Think) 

There isn’t such a thing as “bad bacteria,” per se. The term “bad bacteria” refers to bacteria that do not contribute to overall health and well-being. What’s important is that the population of bacteria in the gut morphs depending on the internal terrain. For example, candida is fine at normal levels. Candida is a fungus that bursts into action when lifestyle factors are out of balance. For people who abuse alcohol or eat too many sugary foods, however, candida overgrowth can be a severe problem. The reason that candida proliferates in this sort of environment is not that it’s necessarily “bad” or harmful. Instead, the overgrowth is due to an abundance of food that candida likes to eat. In a sense, candida is trying to help.

An individual’s diet affects the populations of microbes in the gut in an intricate manner. Eating an ultra-processed diet packed with foods like snacks and sugary juice affects the microbiota population. Energy intake from ultra-processed foods in the US is a whopping 57.9%, meaning that just 42.1% comes from healthy foods. In the first comprehensive review of ultra-processed foods on the gut microbiota, researchers found that eating a diet high in ultra-processed foods changes the composition of the gut microbiota, leading to inflammation and even epigenetic changes. These changes impact the pathophysiology of disease and weight gain. And the effects are transferrable to later generations. 

About the author

Dr. Patrick Lovegrove