The microbiome and its role in immune function

February 8, 2019

 

David Glenn

Zenith News

 

Last month, we touched on inflammation as both a symptom and a cause of autism. We explored how environmental factors that promote epigenetic changes in gene expression might explain the exponential growth in autoimmune disorders over time.

 

We also examined the role that Western diet has on the loss of microbiome diversity in immigrant communities and the dramatic uptick in cases of autism, obesity, etc. in the Somali community here in Minnesota and in Sweden.

 

This month, we take a tour of the microbiome and its role in regulating immune function.  

 

The vast array of organisms that constitute the human microbiome encompasses every branch on the tree of life. Bacteria, fungi, prokaryotes, viruses, and a variety of animalia (mites, nematodes, etc.) have settled into a symbiotic relationship and now call the human body home.

 

Our bodies contain 10 times more non-human cells than those with our distinctive DNA fingerprint and function. Revised estimates have brought that ratio down to around three to one. In exchange for room and board, these creatures provide essential services, such as releasing vital nutrients from the fermentation of indigestible plant fiber.

 

These beneficial cohabitators also compete with and crowd out pathogens as well as controlling the populations of usually benign species that can go rogue and become pathogenic, like E. Coli, when disruptions in diversity occur. The body can sense and communicate with the microbiota via the mesh-like enteric nervous system that lines the gastrointestinal tract. This information is passed on to the vagus nerve and the rest of the central nervous system, completing a feedback loop.

 

The longest nerve in the body, the vagus, plays a vital role in controlling autonomic functions such as breathing, inflammation, insulin signaling, and gut permeability. It is a crucial interface between the various subdivisions of the nervous system. The communication pathway is bidirectional, in that individual species of microflora have demonstrated the ability to modulate inflammation and immune responses to either evade the body’s defenses or attack competing organisms by proxy.

 

Repeated stimulation of the vagus nerve via negative emotional stressors has been shown to alter the makeup and diversity of intestinal communities. It stands to reason that a two-way channel such as this would also allow for disruptions in emotional well-being via signaling aberrations caused by microbiota imbalances or pathogens.

 

A recent study by Oregon State University found a correlation between the ratio of gut bacteria phyla and aggression in dogs. Of the four dominant families of microorganisms, an abundance of Firmicutes species were seen in those dogs displaying higher levels of aggression.

 

Depending on the study reviewed, autistic children are up to three times more likely to experience gastrointestinal issues, such as acid reflux, acquired lactose intolerance, dysautonomia, gastritis, and food sensitivities.

 

A strong correlation between social dysfunction, hyperactivity, irritability, and frequent gastrointestinal flare-ups are seen in both meta-analysis studies and parental reports. Consumption of dairy, certain vegetables, wheat, and processed foods have also been noted by parents as having a negative impact on behavior and digestive issues.

 

A large number of gastrointestinal issues such as Irritable Bowel Syndrome (IBS) are associated with thinning of the epithelial lining in the gastrointestinal tract. There is a correlation between IBS and psychiatric disorders such as depression and anxiety. Furthermore, this thinning of the gut wall is associated with Type 2 diabetes and obesity.

 

The gut lining is maintained through the production of Short Chain Fatty Acids (SCFA). This handful of acids result from the fermentation of indigestible carbohydrates by a variety of organisms in the gut microbiota. Most important of these SCFAs is butyrate, which epithelial cells use as an essential building block and energy source.

 

Butyrate regulates inflammation, macrophage, and T-cell responses by acting as a messenger molecule between the immune system and microbiota. Certain species of Clostridia use SCFAs to regulate the production and storage of Vitamin A in mice, which seems to prevent the immune system from running amok.

 

Loss of microbial diversity, and specifically butyrate-producing organisms, has been observed in patients with IBS as well as autism, diabetes, obesity, various psychiatric and autoimmune disorders. Fecal transfers used to treat antibiotic resistant Clostridium dificile infection (C. Diff) have also been shown to induce both weight gain and weight loss in mice and humans.

 

Development of the microbiome begins in the latter stages of gestation. The first wave of bacterial colonizers is usually transferred from mother to infant during the birthing process. Breastfeeding also transfers a variety of new organisms. Solid foods populate the gut with even more symbiotic microbes.

 

These transitions in dominant bacteria continue through exposure to the environment until the child reaches three years of age. Factors affecting the development of a diverse and stable microbiome include antibiotic treatment, formula feeding, cesarean delivery, as well as early exposure to allergens and an outdoor environment.

 

Note that the age at which synaptic pruning begins, microbiome stability is achieved, conceptual language skills develop, and the signs of autism appear is concurrent.

 

Wonder where this is going or think you have an idea? Pick up a copy of the Zenith next month and follow this story as it as explores the role that bees, berries, diet, and dirt might play in microbiome diversity.

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