The Fascinating Link Between Type-1 Diabetes and the Human Gut

Interesting connections between our microbiomes and auto-immune disease like diabetes.

It has been widely reported that auto-immune diseases, including Type-1 Diabetes, are on the rise world-wide. In an auto-immune disease, the immune system goes awry and launches an attack against the person’s own cells, misidentifying them as a threat to attack.

So why is it that in our developed world, where we have better access to nutrition, modern sanitation and advanced medical care, that auto-immune diseases such as Type-1 Diabetes are becoming more prevalent? Increasingly, doctors are coming to believe that there is a connection between the health of the gut microbiome and the increasing rates of Type-1 diabetes.

This article will: examine the science behind the association between Type-1 diabetes and the health of the gut microbiome; look at how our modern world may be affecting the gut microbiome and leading to increased rates of Type-1 diabetes; and explore the science and logic behind how improving microbial health might prevent or delay the onset of Type-1 diabetes in those who are at risk of getting it.

Type-1 Diabetes

Diabetes is generally classified into two branches known as Type 1 and Type 2 diabetes.

Type-1 diabetes, also known as Juvenile Diabetes or Insulin-dependent diabetes is an auto-immune disease in which the pancreas no longer produces (or produces in insufficient quantity) the hormone insulin. Insulin enables sugar to enter the cells of the body where it can be made into energy. When the sugar cannot enter the cells, it builds up in the bloodstream and causes lots of harm including blindness, and life-potentially deadly complications such as cardiovascular disease and kidney damage.

There is a strong genetic component to this condition. However, genetics alone do not entirely explain its incidence as some people with a genetic susceptibility to the disease do not develop it. Studies involving identical twins have show that if one twin develops the condition, the other twin has lower than 35% likelihood of also contracting Type-1 diabetes. Therefore, something in addition to genes is triggering the disease in people in those who have a predisposition to it.

The rate of Type-1 diabetes has been rising dramatically – increasing 7 fold in the last fifty years alone Type-1 diabetes has been accelerating faster in certain parts of the world than others. Something in addition to heredity must be triggering this rise, as migration studies have confirmed that when people emigrate from low-incidence parts of the globe to high-incidence regions, they and their descendants show an increased risk of developing the disease – corresponding more to where they have moved to and not where their ancestors (and genes) came from.

Although the disease most commonly begins in childhood or adolescence, it can also emerge in adulthood. It is triggered when a person’s immune system, mistakenly perceiving them as a threat, attacks and destroys the insulin producing cells (called “islet” cells) in the pancreas. Monitoring levels of sugar in the blood frequently and taking supplemental insulin can prevent some of the worst effects of the disease, while also increasing life expectancy. There is no known cure for Type-1 diabetes.

It is becoming clear to those who study the issue that changes to the microbes that make up the gut microbiome affect the development of Type-1 diabetes. For that reason, the human microbiome has become a promising area for ongoing medical research that may provide new hope for prevention of diabetes as well as providing encouraging avenues to explore for additional treatments and a possible cure.

Changes to Gut Microbiome Associated with Type-1 Diabetes

Medical science has recognized for some time that the guts of people with Type-1 diabetes are missing healthy microbes. This can be seen both in lower numbers overall of microbes and also in a reduced diversity of species (different types) of microbes that are particularly associated with good health. However, science, at this point, does not know whether (1) the diabetes is causing the reduction in healthy gut microbes, (2) the reduction in the healthy microbes is triggering the diabetes or (3) whether some other unrelated factor is causing both things to happen independently of each other. Recent studies are starting to shed light on this fundamental question of causation.

Additionally, doctors have observed that patients with Type-1 diabetes have higher gut permeability than what is expected in healthy patients. The gut normally provides a tight barrier to prevent substances in the digestive tract from leaking out into the abdominal cavity and the blood stream. Where there is increased permeability (sometimes referred to as a “leaky gut”), foreign substances can seep into the body where they cause inflammation. Inflammation is the body’s immune system response to a trigger – here the substances that are leaking out of the gut. Long-term inflammation can lead to disease.

One of the many beneficial functions that our gut microbiome provides us, is to line the digestive tract and to strengthen the impermeability of the gut. One possibility is that the alterations to the permeability of the gut lining seen in the gut in Type-1 diabetes are created by the imbalances of the gut microbes.

Auto-immune diseases, like Type-1 Diabetes, are thought to involve chronic inflammation. Since many Type-1 diabetes patients have microbiomes that are lacking important microbes and many also have leaky guts, which we know cause inflammation, medical science is now exploring the link between Type-1 diabetes and the microbiome.

Does an Unhealthy Gut Microbiome Lead to Type-1 Diabetes?

Doctors are attempting to figure out whether the changes that are occurring in the gut could be causing Type-1 diabetes and whether manipulating the gut microbiome could delay onset of Type-1 diabetes in individuals who are at high risk for the disease.

Differences in Microbial Inhabitants

A group of researchers decided to examine the specific compositions of microbes in the gut microbiomes of children with Type-1 diabetes and in children without it. They found out that the two groups had quite different microbial inhabitants. The study controlled for breast-feeding and mode of delivery (C-section vs. vaginal) in the participants to ensure that those two factors, which are known to alter the mix of microbes that colonize the intestinal tract in children, did not distort the results.

The results showed that the diabetic children had lower levels of Bifidobacterium, Lactobacillus and Clostridium bacteria than did the healthy children. These three species are known to promote human health and play an important role in preventing gut permeability (and thus inflammation caused by a leaky gut). So, this is a significant finding.

The researchers also observed differences in the ratio of Firmicultes to Bacteroidetes bacteria in the diabetic versus the healthy children. Studies on obesity have found that the ratio of these two species in the gut can affect how much energy is extracted from food and the researchers believe this altered ration may affect blood sugar levels in the diabetic children.

An ambitious, long-term prospective study was conducted to examine the changes in the gut microbiome prior to the onset of Type-1 diabetes in children. Medical researchers conducted periodic evaluations of the composition of the gut microbiome in children who were genetically at risk for Type-1 diabetes from birth to age 3. They did this by evaluating which microbes were present in fecal samples that were collected. In the small number of children who did go on to develop the disease during the study, the researchers noticed that they had a 25% drop in the diversity (number of different species) of gut microbes that occurred one year prior to the onset of the disease. Also one year prior to the diagnosis of the disease, researchers observed a change in the ratios of the different species of microbes in the guts of the children who went on to get sick – there was a disproportionate decrease in bacteria known to help promote gut health, and a simultaneous increase in bacteria that are known to promote inflammation. As mentioned above, Type-1 diabetes is a disease that involves chronic inflammation.

Dr. Jessica Dunne, the Director of Discovery Research at JDRF (the funder of the study) said, “We know from previous human studies that changes in gut bacterial composition correlate with the early development of type 1 diabetes, and that the interactions between bacterial networks may be a contributing factor in why some people at risk for the disease develop type 1 diabetes and others don’t.” This is the first study to show how specific changes in the microbiome are affecting the progression to symptomatic T1D.”

C. Section, Limited Breast Feeding and Early Antibiotics

A babies’ microbiome evolves after birth and during the first months of life. Method of birth, duration of breast-feeding and early exposure to antibiotics all impact the make-up of microbes that colonize a young child’s gut. Each of these factors has been linked to alterations in the number and diversity of microbes in a child’s gut. Coincidentally or not, these three factors have also been linked to increased rates of Type-1 diabetes.

A healthy and diverse gut microbiome trains the immune system. It also teaches the immune system to identify which cells are “self” versus “other.” This is important to preventing auto-immune disease, such as diabetes, in which the immune system attacks the body’s own insulin-producing cells.

A healthy microbiome also calms inflammation, which as we have mentioned, is a factor in diabetes.

For these reasons, those who study this issue believe that a relatively poor microbiome in babies may be contributing to higher rates of Type-1 diabetes.

Cesarean Section

It has been shown that human children born via Cesarean section are more likely to go on to develop Type-1 diabetes, with a 20% increased risk of the disease as compared to their vaginally delivered peers.

Travelling through the birth canals swathes the baby in her mother’s vaginal microbes. The mix of these microbes evolves throughout pregnancy in preparation for the birth, becoming higher in microbes that are optimal for colonization of the baby’s digestive tract. The infant literally breathes them in and swallows them, where they go on to make up the bulk of the early microbiome.

Infants born via C. section do not receive the same microbial bath and have been shown to have lower numbers and diversity of microbes in their digestive tracts that tend to persist over time – one study found that the microbiome disturbances seen in these babies can persist for 7 years.

Breast-feeding

Breast feeding a child is another important way that healthy bacteria are transferred from mother to child, where they go one to colonize the infant’s gut and train her developing immune system. Breast-fed babies have been shown to have healthier and more diverse microbial communities than their primarily formula-fed peers. Certain studies have suggested that short duration of breast-feeding case increase risk of Type-1 diabetes.

Antibiotics

The development of antibiotics is one of the major reasons that life-expectancies increased so dramatically during the 1900’s. They work by killing bacteria, both the good ones and the bad. When healthy bacteria are killed, antibiotic-resistant or harmful ones, can move in to the vacated real estate in the gut. Yeasts, that can be healthy in smaller numbers but can cause problems in higher amounts, also tend to proliferate following a course of antibiotics.

Because the microbiome is still developing and is unstable in infants, courses of antibiotics early in life are particularly disruptive to the colonization of the healthy microbiome and the training of the immune-system that the good microbes provide. Antibiotics can be life-saving, but they are not without side-effects – one of them being the harm they can cause to the establishment healthy microbes in the gut and thereby disturb the development of the immune system.

Repeated exposure to antibiotics early in infancy has been correlated with an increased risk of developing Type-1 diabetes.

Can Altering our Gut Bugs Affect the Onset of Type-1 Diabetes?

The knowledge that gut microbes alter in both number and type prior to the onset of disease is very intriguing to diabetes researchers. The results of earlier studies showing links between the make-up of gut bacteria and the incidence of Type-1 diabetes has caused them to wonder whether they could cause or prevent the onset of Type-1 diabetes by deliberately altering the gut microbiomes of subjects at genetic risk for the disease.

In animal studies, researchers raised non-obese, but genetically prone to diabetes (NOD) mice in a germ-free environment, meaning their guts contained no bacteria at all. These rats had a much higher incidence of Type-1 diabetes than the control group of NOD mice raised in a regular, germ-filled environment. Conversely, non-sterile NOD mice given antibiotics prior to the onset of diabetes showed reduced rates of the disease from the control group. Taken together, these studies lend weight to the theory that certain microbes play a role in triggering Type-1 diabetes while other species of microbes have a protective role against the disease and that manipulating the microbial mix could increase or decrease rates of the disease.

In another study, researchers gave probiotic supplements to NOD rats. The results showed that giving the probiotic supplement VSL#3 (a mixture of Bifidobacterium and Lactobacillus species and Streptococcus salivarius subsp. thermophilus) both reduced the incidence of and also delayed the onset of the rodent-version of Type-1 diabetes in lab rats.

In yet one more rodent study, giving rats a low fat diet supplemented with the probiotic bacteria Lactobacillus seemed to reduce the incidence diabetes in the animals.

These results are intriguing, but rats are not humans and more research is needed before this research can start to offer real promise to people at risk for developing Type-1 diabetes.

Could Microbes “Cure” Type-1 Diabetes?

Researchers at Cornell University have shown that this intriguing concept may one day become a reality.

They genetically engineered a particular type of probiotic bacteria that secretes a hormone capable of converting both rat and human epithelial cells (cells that line the cavities of the body) into insulin secreting cells, similar to those that are destroyed by Type-1 diabetes. They then fed these specially created microbes to NOD rats.

The rats subsequently developed insulin-producing cells in their small intestine capable of producing 25-35% the amount of insulin found in non-diabetic rats. Amazing! Although these bacteria do not replace the islet cells destroyed by the disease, they can perform the same function – providing the necessary insulin.

The next challenge will be increasing the production of insulin by these microbes to levels required for optimal health. More importantly, the long-term efficacy and more importantly the safety of this approach must be tested and confirmed. This will take time, unfortunately.

Where Does this Leave Us?

Given the success seen in altering the microbiome of rodents to prevent, delay onset of or even treat Type-1 diabetes, more extensive human studies are necessary to see if the same beneficial effect can be shown for us.

Human studies are ongoing, but are difficult to conduct as Type-1 diabetes typically arises in childhood so the studies will require child volunteers who are genetically susceptible to the disease, but who have not yet gotten sick. Not only will it be challenging to locate sufficient numbers of these children it will also be exceedingly tough to find parents who are willing to let them participate and able to comply with the study’s requirements.

However, in the meantime, there are still steps that one can take to promote a healthy microbiome that may perhaps provide some benefit in staving off a genetic susceptibility to the disease. Type-1 diabetes is associated with a changed microbiome and with increased permeability of the gut (“Leaky Gut Syndrome”) leading to low-grade inflammation. Making life-style changes to maintain the heath of the gut microbiome might be able to prevent or even treat a leaky gut and the resulting inflammation that is associated with Type-1 diabetes. Here are some ways to do so.

Diet. Eat to support a heathy microbiome. A low-fat, high fiber diet supports a healthy microbiome. Unpasteurized fermented foods such as sauerkraut, kimchi, pickles, buttermilk, cheese and kefir can provide high doses of healthy probiotics. Taking a probiotic supplement can temporarily increase the numbers of beneficial microbes. Limit foods with preservatives or other chemical additives that can harm the microbiome.

Unnecessary Medical Interventions. We know that both antibiotics and cesarean section can alter the microbiome in unhealthy ways. Relying on these treatments only when necessary will reduce harm to the microbiome, particularly for infants who are at genetic risk for Type-1 diabetes. Exclusive breast feeding for the recommended duration can supplement the baby’s microbiome with healthy microbes, which can be particularly important if a genetically pre-disposed baby was born via C. section or was treated with antibiotics.

Alcohol, Stress and Exercise. Excessive alcohol use hurts our healthy microbes, so consider their health the next time you reach for your third glass of wine. So, too, does prolonged stress. Alternatively, exercise promotes the growth of our healthy gut bugs so consider replacing a few beers after a long, hard day’s work with a brisk walk through the neighborhood instead.

Although in the worst case these changes may not affect the onset of Type-1 diabetes, they will certainly do no harm. A healthy microbiome supports your immune system, aids in digestion and vitamin synthesis, prevents obesity, supports mental health, and even reduces allergies. This is nothing to sneeze at!

Given the toll that Type- 1 diabetes can take on the body and the impact that constantly managing blood sugar has on quality of life, taking these practical steps to increase gut health, particularly if you are genetically susceptible to the disease, seems like good common sense.

If you have read this far, you likely care a great deal about this issue, which has not been covered extensively in the main-stream press. Please share your own thoughts in the comments below.

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