DIABETES: The Bacteria Connection

Gut microbiota composition early in life can affect adult health status including obesity, diabetes, heart and autoimmune disease susceptibility. A team of scientists from Copenhagen and Beijing examined gut bacteria composition of both diabetic and healthy people. The bacteria markers or indicators of people with type 2 diabetes were markedly different from healthy subjects.  Studies by other researchers comparing bacteria composition in the mouth and on the skin of people with and without diabetes also found certain bacteria were more prevalent in diabetic people. These preliminary studies found certain bacteria were associated with both Type 1and Type 2 Diabetes but were not sure whether the bacteria actually cause diabetes or were opportunistic infection since high blood sugar encourages bacteria growth. Other studies on specific bacteria species demonstrated they actually promoted the development of the disease.

Since specific bacteria can cause diabetes, some researchers wondered whether there were other bacteria that can protect against the development of the disease. A team of researchers from France, China and Sweden transferred gut microorganisms from healthy mice to mice with type 1 Diabetes, an autoimmune disease. That reduced the occurrence of diabetes.  The researchers observed, "This research is further evidence of the undeniable role microbiota plays in autoimmune diseases, particularly in controlling the development of autoimmune diabetes." [Study presented at  la recherche médicale]

Microbes & Type 1Diabetes

Type 1 Diabetes (T1D) is an autoimmune disease where inflammation in the Pancreas resulted in certain cells in the immune system attacking beta pancreatic cells that secrete insulin. The damaged, failing beta cells could not produce enough insulin, resulting in insulin deficiency.

An increasing body of research demonstrated that the bacteria in our gut (microbiota) can influence our immune system and inflammation status.

A small human study compared the microbial composition in relation to blood glucose level of T1D versus healthy non-diabetic children. researchers found that the ‘good bacteria’, Bacteroidetes, decreases significantly as blood glucose level increases while  The ‘bad bacteria’, Clostridium, increases significantly as blood glucose level increases in diabetic children. Healthy children have significantly more Bacteroidetes.

“At the genus level, we found a significant increase in the number of Clostridium, Bacteroides and Veillonella and a significant decrease in the number of Lactobacillus, Bifidobacterium, Blautia coccoides/Eubacterium rectale group and Prevotella in the children with diabetes.” The authors added, “Moreover, the quantity of bacteria essential to maintain gut integrity was significantly lower in the children with diabetes than the healthy children.” Since children with diabetes have a higher level of blood sugar compared to the healthy group, the researchers suggested the increase of ‘bad bacteria’ may be related to the glycemic level in the group with diabetes. The study showed Type 1 Diabetes is associated with compositional changes in gut microbiota. [Maria Isabel Queipo et al.]

Viruses are associated with T1D as well. In boys, human parechovirus infection induces a subsequent appearance of diabetes-associated autoantibodies.

Echovirus 4 and Coxsackie B virus are associated with T1D as well. The latter may infect and destroy the insulin producing beta-cells in the pancreas and also damage these cells via indirect autoimmune mechanisms. However, Coxsackie B3 and B6 viruses were found to be associated with a reduced risk of such autoimmunity (possibly due to immune cross-protection against Coxsackie B1 virus).

Not all bacteria and viruses within a particular species are pathogenic. Some are commensal (benign). A Finnish study compared different strains of  Bifidobacteria And found that children who developed islet autoimmunity and T1D later in life showed significantly higher responses and have significantly higher autoantibodies against a bacteria strain, Bifidobacteria adolescentis DSM 20083 proteins .

The researchers pointed out, biochemically detectable autoantibodies can serve as reliable indicator for T1D development. [I Talja - 2014]

Type 1 Diabetes Prediction

If you have a family history of Type 1 Diabetes (T1D), have the immediate family (including children), screened for the disease. This is to identify anyone who may have Latent autoimmune diabetes of adults (LADA) that will rear its ugly head years later.

A study by   nip et al. demonstrated that all children initially tested positive for diabetes-associated autoantibodies (GADA and IA-2A) progressed to clinical Type 1 Diabetes over a 26-year follow-up.

These auto antibodies can be used efficiently for the prediction of T1D in first-degree relatives of affected patients with high probability of developing the disease over the subsequent 27 years according to European Union studies. Therefore, screening people with a family history of T1D can serve as prediction of future need for insulin treatment in adult-onset diabetes.

In USA and Europe, the frequency of autoantibodies against IA-2 ranges between 60 to 80% in newly diagnosed T1D children. This figure dropped to around 45% in those diagnosed after the age of 20.

The presence of GADA appears to increase with age. Therefore, the latter can be used to identify autoimmune diabetes in adults masquerading as type 2 diabetes. Moreover, the presence of GADA   can predict progression to Type 1 Diabetes for adults   who do not have any signs of the disease (LADA).

Related article: Type 2 Diabetes & Insulin Resistance

Protection against Type 1 Diabetes (T1D)

Cells in our colon produce antimicrobial peptides (peptide antibiotics)  called cathelicidins  that protect us against disease-causing microbes  (pathogens) and can modulate our immune system  against several autoimmune diseases. Scientific studies found that  beta pancreatic cells in healthy mice produce cathelicidins whereas this function was impaired in diabetic rodents.

Since T1D is an autoimmune disease, a  research team coordinated by Julien Diana decided to find out whether cathelicidins   can control type 1 diabetes. They injected diabetic mice with cathelicidins.

"Injecting cathelicidins inhibits the development of pancreatic inflammation and, as such, suppresses the development of autoimmune disease in these mice" states Julien Diana.

Short-chain fatty acids (SCFA) produced by good gut bacteria (probiotics) modulates the  production of  cathelicidins.  Given that diabetic mice have  a lower level of short-chain fatty acids compared to healthy mice, the  cathelicidins deficiency in diabetic mice may be due to insufficient SCFA. The team  transferred part of the gut bacteria from healthy mice to diabetic mice, and  thus re-established a normal level of cathelicidin. Meanwhile, the transfer of micro-organisms reduced the occurrence of diabetes. This experiment highlighted the important role good microbes play in the prevention of autoimmune diseases such as autoimmune diabetes.

[Immunity- August 2015]

The above experiment together with other preliminary studies suggested probiotics together with a diet that that encourages growth of these bacteria may be a possible way to protect against Type 1 Diabetes.