Type 1 diabetes is an autoimmune disease characterised by antibodies directed at the pancreatic beta cells. Unchecked this autoimmune process impairs the pancreas’s ability to produce insulin resulting in poor blood sugar control and hyperglycaemia. This article will explore the gut microbiota and the changes that disrupted gut flora, or dysbiosis, has on the onset and development of type 1 diabetes.
Genes, Environment and a Trigger
The onset of type 1 diabetes generally occurs in children of 5-7 years old and can be progressing without any symptoms for months to years before proper diagnosis. Fasted blood sugar levels are used as a primary marker for diagnosis along with a blood test that measures glycated haemoglobin (sugar molecule bound to a protein molecule, in this case haemoglobin) called haemoglobin A1C (1).
Genetics definitely play a role in the progression of autoimmune diseases such as type 1 diabetes. But can we solely blame our genetic makeup? Many researchers would disagree. Alessio Fasano lays out three important factors for the progression of autoimmune disease to take place. First off he lists genes. Nothing surprising there. Then he lists environment. The thinking behind this requirement revolves around antigenic exposure. Finally the genetically susceptible person must be exposed to the antigen. This can be referred to as a ‘trigger’. Case and point would be celiac disease. A person celiac disease experiences an autoimmune reaction to the ingestion of gluten. Remove the gluten remove the trigger. Fasano proposes that intestinal permeability, or leaky gut, also needs to be present for an autoimmune disease to progress. (2).
An antigen is any substance that causes your immune system to produce antibodies against it. This means your immune system does not recognize the substance, and is trying to fight it off (3).
Back to type 1 diabetes.
Type 1 Diabetes And The Gut
As with many diseases the gut microbiome is involved. As it is such early days it can be hard to determine whether an imbalanced gut microbiome is the driver, the result of another physiological process or one of many contributing factors that eventually ends up with the disease manifesting in the body. One review summarised the different animal studies that have showed an imbalanced gut ecosystem with elevated Bacteroides spp. and diminished Lactobacillus and Bifidobacterium spp.
The increased levels of Bacteroides are theorised to create a proinflammatory immune response due to the the endotoxins found on their outer membranes known as lipopolysaccharide or LPS (4). A controlled study confirmed this by showing significantly elevated endotoxins in type 1 diabetics blood samples compared to healthy controls.
Human studies have echoed the thinking that a disrupted gut microbiome is present during the progression of type 1 diabetes. One studied tracked 4 Finnish children with a predisposition to type 1 diabetes and 4 healthy children with no genetic susceptibility. Stool samples were compared between the two groups over a period of time showing a steady increase in the Bacteroidetes phylum (in which the Bacteroides genus falls in) and a decrease in the Firmicutes phylum. Digging into the microbiome at the species level (much more helpful) we can see a decrease in the beneficial bacteria Faecalibacterium prausnitzii. As we have discussed before this bacteria has been shown to be anti inflammatory, improves leaky gut by reducing permeability and may increase T regulatory white blood cells which help to keep the autoimmune process in check.
Another study looked at the differences in the gut flora from 16 children with type 1 diabetes and 16 healthy controls. Again they found a decrease in Firmicutes phylum and an increase in Bacteroides genus. They also found lower Bifidobacterium and Lactobacillus species in the type 1 diabetic group. So we are starting to paint a picture here. A disrupted gut microbiome has been shown to be concurrently progressing along with type 1 diabetes.
Is It All About Fermentation?
We have covered the short-chain-fatty acid production by the fermenting gut microbes many times in the past. It keeps coming up time and time again in the research and literature on the gut microbiome in health and disease. Unsurprisingly it comes up again in relation to type 1 diabetes and gut health. Looking at the gut flora from 18 children with type 1 diabetes susceptibility they found lower levels of Bifidobacterium adolescentis, Faecalibacterium prausnitzii, Clostridium clostridioforme and Roseburia faecis which are all fermenters that produce short chain fatty acids such as butyrate (8).
The progress of the gut microbiome, from birth, through the formative years and into adulthood is a story for another article. What is worth covering here is the influence that one specific bacterial microbe can have on the development of the gut. Bifidobacterium longum subspecies infantis (Bifidobacterium infantis) colonises the gut in the very early days, possibly even before birth, and is fed specifically by the prebiotics present in breastmilk known as human milk oligosaccharides. Bifidobacterium infantis is thought to contribute to health by being anti-inflammatory, decreasing intestinal permeability and occupying space so that other microbes can’t take hold and grow (9). Why is this relevant to our discussion on type 1 diabetes? A recently published article in the Pediatric Diabetes Journal discusses the disappearance of the Bifidobacterium genus and in particular Bifidobacterium infantis even in breastfed, vaginally delivered infants. They associate the loss of this one particular microbe, and the health providing benefits it imparts to the infant, with the rise in type 1 diabetes.
Where To From Here
Drawing any actionable information from these studies can be difficult. There haven’t yet been any interventional studies done on gut health and type 1 diabetes (although one is planned). With that disclaimer out of the way I think it is always wise to mind your microbiome. Prebiotics have a very potent way of shifting the gut flora in a healthy direction, although a small subset of people don’t tolerate them well. Certain probiotics have been shown to help by improving intestinal permeability (11) tone the immune system (12).
Specific to the onset of type 1 diabetes, Saccharomyces boulardii (particularly the Biocodex strain), a probiotic yeast has been shown, in-vitro, to exert anti-inflammatory effects on certain proinflammatory cell activation mechanisms stimulated by LPS. Assuming that this translates to humans then Saccharomyces boulardii Biocodex would be a powerful tool to dampen down the immune response that is becoming dysregulated (13).
References and Resources
- Type 1 diabetes
- Leaky Gut and Autoimmune Diseases
- medline plus
- Gut Microbiota and Type 1 Diabetes
- Increased levels of ligands of Toll-like receptors 2 and 4 in type 1 diabetes
- Toward defining the autoimmune microbiome for type 1 diabetes
- Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case-control study
- Fecal Microbiota Composition Differs Between Children With b-Cell Autoimmunity and Those Without
- Bifidobacterium longum subspecies infantis: champion colonizer of the infant gut
- Prospects for Primary Prevention of Type 1 Diabetes by Restoring a Disappearing Microbe.
- Lactobacillus plantarum MB452 enhances the function of the intestinal barrier by increasing the expression levels of genes involved in tight junction formation
- Effects of Saccharomyces boulardii on Intestinal Mucosa
- Saccharomyces boulardii inhibits lipopolysaccharide-induced activation of human dendritic cells and T cell proliferation