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.

 

Using Bacteria To Program Your Brain

Researchers have found that the bugs in your gut can influence your brain’s responses. Working with germ-free rodents, they discovered the animals’ behavior changed when certain germs were introduced into their gut through their diet. Intrigued, other universities tested the effect of beneficial bacteria (probiotics) on people’s mood and found that the gut bacteria consumed by participants actually changed their mood. This was verified by brain scans, blood and urine tests for chemicals produced by the body that influenced mood and physiological responses.

Considering that microorganisms in our gut outnumber cells in our body ten to one, it is not surprising that the chemicals that they produced could travel to our brain and alter our brain function. In fact, our Central Nervous System (CNS) only produces five percent of serotonin, a neurotransmitter that influences mood, memory, learning, digestion, sleep and sexual desire activities. The remainder 95 percent is manufactured by gut bacteria. Communication and sharing of chemicals go both ways between our brain and microbes. The result is reflected through mood and behavior.

Besides brain chemistry, this invisible army of workers in our gut also influences inflammation and pain perception, the body responds to stress, modulates our immune system and even help ‘program’ some aspects of brain development through influencing neural development.

Bacteria-Brain Communication

While harmful bacteria (pathogens) can jack up anxiety and depression, the good bacteria (probiotics) calms you down and lift your mood. This is because bacteria in our gut and our brain are constantly sending messages to each other through a number of channels.

1. Our IMMUNE CELLS are like the police force, constantly patrolling our body for break-ins, invasion and attack by pathogens and foreign substances. This police force and the chemicals they synthesize are used as messengers.

2. Sometimes gut bacteria use the vagus nerve to communicate with the brain. Researchers in Ireland fed Lactobacillus to mice that resulted in behavior change. When they cut the vagus nerve (the neural conduit between gut and brain) in mice, the effect that Lactobacillus exerted earlier on brain biochemistry, stress response and behavior evaporated.

3. The third method of communication is through neurochemical. Gut bacteria and brain produce and respond to the same neurochemicals (neurotransmitters).

A joint Duh-British Pediatric Research published in Nature pointed out, “Accumulating evidence has suggested the importance of the gut microbiome in this bidirectional communication system and as a result, the concept of the microbiome-gut-brain axis has emerged.” [Manon J. N. L. Benders]

Research into this exciting new field is still preliminary. Scientists still have to ascertain which bacterial strains are absolutely vital to mental functioning, or whether a combination of bacteria in the right balance is needed to influence mental functioning.